全文获取类型
| 收费全文 | 2712篇 |
| 免费 | 103篇 |
| 国内免费 | 21篇 |
学科分类
| 医药卫生 | 2836篇 |
出版年
| 2023年 | 9篇 |
| 2022年 | 17篇 |
| 2021年 | 35篇 |
| 2020年 | 21篇 |
| 2019年 | 22篇 |
| 2018年 | 41篇 |
| 2017年 | 22篇 |
| 2016年 | 20篇 |
| 2015年 | 42篇 |
| 2014年 | 50篇 |
| 2013年 | 83篇 |
| 2012年 | 164篇 |
| 2011年 | 189篇 |
| 2010年 | 84篇 |
| 2009年 | 97篇 |
| 2008年 | 195篇 |
| 2007年 | 203篇 |
| 2006年 | 219篇 |
| 2005年 | 192篇 |
| 2004年 | 215篇 |
| 2003年 | 200篇 |
| 2002年 | 202篇 |
| 2001年 | 31篇 |
| 2000年 | 16篇 |
| 1999年 | 37篇 |
| 1998年 | 53篇 |
| 1997年 | 58篇 |
| 1996年 | 33篇 |
| 1995年 | 23篇 |
| 1994年 | 22篇 |
| 1993年 | 25篇 |
| 1992年 | 17篇 |
| 1991年 | 10篇 |
| 1990年 | 12篇 |
| 1989年 | 21篇 |
| 1988年 | 11篇 |
| 1987年 | 14篇 |
| 1986年 | 18篇 |
| 1985年 | 12篇 |
| 1984年 | 15篇 |
| 1983年 | 11篇 |
| 1982年 | 8篇 |
| 1981年 | 14篇 |
| 1980年 | 9篇 |
| 1979年 | 12篇 |
| 1978年 | 5篇 |
| 1977年 | 4篇 |
| 1976年 | 4篇 |
| 1973年 | 3篇 |
| 1972年 | 3篇 |
排序方式： 共有2836条查询结果，搜索用时 31 毫秒
991.
Platelet microparticles and vascular cells interactions: a checkpoint between the haemostatic and thrombotic responses 总被引：1，自引：0，他引：1
Described 40 years ago as cell dust, microparticles (MPs) are now considered a key component in the haemostatic response. Owing to their plasma membrane reactivity, platelets are believed to constitute the main source of circulating procoagulant microparticles and behave as true sensors for the haemostatic response. Erythrocytes, leukocytes and endothelial cells are also able to shed MPs in the blood flow, their respective contribution varying with the pathophysiologic circumstances and extent of the cellular damage. The catalytic properties of MPs rely on a procoagulant anionic phospholipid, phosphatidylserine, made accessible at the outer leaflet following plasma membrane remodelling and on the eventual presence of tissue factor (TF). Under resting conditions, most membrane-bound TF is encrypted. Although able to bind to FVIIa, it does not trigger blood coagulation. Under prothrombotic conditions, TF decryption would occur through intricate pathways involving platelets, monocytes, endothelial cells and derived MPs. P-selectin/P-selectin glycoprotein Ligand-1 (PSGL-1) interactions and reactive oxygen species would promote TF decryption in cell-MP aggregates. At sites of endothelium injury, the swift recruitment of TF+-MPs through P-selectin/PSGL-1 interactions enables the concentration of TF activity above a threshold allowing coagulation to be triggered. Another crucial feature in the initiation of blood coagulation, possibly tuned by MPs, is the balance between TF and TFPI. In specific pathophysiologic contents with elevated levels of circulating TF+-MPs, accessible TFPI at the MP surface would be overwhelmed. Beyond their procoagulant properties demonstrated in vitro, a number of pieces of evidence points to procoagulant MPs as efficient effectors in the haemostatic response, and as pathogenic markers of thrombotic disorders and vascular damage. This review will focus on the pathophysiological significance of platelet-derived MPs and their interaction with vascular cells. 相似文献
992.
Maceo BM Manns F Borja D Nankivil D Uhlhorn S Arrieta E Ho A Augusteyn RC Parel JM 《Journal of vision》2011,11(13):23
The purpose of this study was to determine the contribution of the gradient refractive index to the change in lens power in hamadryas baboon and cynomolgus monkey lenses during simulated accommodation in a lens stretcher. Thirty-six monkey lenses (1.4-14.1 years) and twenty-five baboon lenses (1.8-28.0 years) were stretched in discrete steps. At each stretching step, the lens back vertex power was measured and the lens cross-section was imaged with optical coherence tomography. The radii of curvature for the lens anterior and posterior surfaces were calculated for each step. The power of each lens surface was determined using refractive indices of 1.365 for the outer cortex and 1.336 for the aqueous. The gradient contribution was calculated by subtracting the power of the surfaces from the measured lens power. In all lenses, the contribution of the surfaces and gradient increased linearly with the amplitude of accommodation. The gradient contributes on average 65 ± 3% for monkeys and 66 ± 3% for baboons to the total power change during accommodation. When expressed in percent of the total power change, the relative contribution of the gradient remains constant with accommodation and age in both species. These findings are consistent with Gullstrand's intracapsular theory of accommodation. 相似文献
993.
Minja Coelho;Jean-Marie Tan;Natalie Ling; 《The Australasian journal of dermatology》2024,65(3):e30-e33
Jacquet erosive dermatitis (JED) is a rare, severe form of napkin dermatitis associated with friction and irritant exposure in the napkin area. The condition typically causes erosions and erythematous punched-out ulcerations. We present two cases of JED in infants associated with the use of a common brand barrier cream Curash. This appeared to present following a change of several active ingredients. 相似文献
994.
Jean-Marie Michot Maxime Annereau Alina Danu Clémence Legoupil Louis Bertin Claude Chahine Nadia Achab Anna Antosikova Ariane Cerutti Julien Rossignol David Ghez Christophe Willekens Peggy Dartigues Julien Lazarovici Francois Lemare Vincent Ribrag 《European journal of haematology》2020,104(4):281-290
995.
Jean-Marie R. Peron Hollie Packman William J. Peveler Joseph C. Bear 《RSC advances》2020,10(23):13369
We have investigated the in situ formation of Low Molecular Weight Organogelator (LMWO) molecules in oil-on-water slicks through dual reactive precursor injection. This method alleviates the need for any carrier solvent or prior heating, therefore reducing the environmental impact of LMWOs, giving instantaneous gelation, even at low temperatures (−5 °C). We show minimal leaching from our gels into the water layer.Instantaneous gelation: a reactive precursors approach for the near-instant gelation of oil-on-water slicks down to −5 °C.Low molecular weight organogelators (LMWOs or LMOGs) are small molecules designed to form supramolecular networks on addition to oil, turning the oil into a solid gel.1–5 Once gelled, the oil can then be more easily removed. This makes LMWOs of great interest in the clean-up of marine oil and fuel spills, especially close to the shoreline or on bodies of inland water. A key advantage of LMWOs is that their properties can be designed to some extent at a molecular level4 insofar as one must ensure that the molecule will be able to form a supramolecular network with itself as well as ensuring solubility in the oil. Fig. 1(a) and (b) show the urea-based LMWOs used in this work, with hydrogen bonds between urea groups and π–π stacking between aromatic groups as examples of gelling intermolecular forces shown in Fig. 1(c). The lipophilic part of the LMWO grants the molecule solubility in oil as typically, the gelling intermolecular forces are polar in nature. Therefore, the synthesis of LMWOs often relies on balancing solubility in oil with polar intermolecular forces; too much hydrogen bonding, the compound will not be easily soluble, too little, and the compound simply will not gel.Open in a separate windowFig. 1(a) Reaction scheme of p-tolyl isocyanate “core” with a diisopropylamine “tail” forming N′-(4-methylphenyl)-N,N-dipropan-2-ylurea (referred to as compound 1), (b) reaction of p-tolyl isocyanate with dodecylamine forming N-dodecyl-N′-(4-methylphenyl)-urea (referred to as compound 2) (c) a scheme demonstrating the hypothetical self-assembly of urea-based LMWOs into supramolecular networks.Tolyl-isocyanates (“core” groups) are attractive precursors for urea based LMWOs, due to their ready availability from widespread use in poly(urethane) manufacture. They produce urea/urethane moieties on reaction with a nucleophile such as an amine or an alcohol, which readily hydrogen bond, giving the gelator the required intermolecular forces to form the supramolecular network in oils. These urea-based LMWOs have been widely characterised and explored.1–4 The choice of nucleophilic “tail” (amine) is critical in order to impart solubility to the LMWO whilst still allowing the self-assembled structure to form. Previously, we have demonstrated a selection of p, m and o-tolyl isocyanates forming stable oil binding gels in sea water.9 In this study we examined the properties of a diisopropylamine/p-tolyl isocyanate system (Fig. 1(a)), and a dodecylamine/p-tolyl isocyanate system (Fig. 1(b)) with an eye to in situ application of the gel to an oil spill.It is the delivery of the LMWO to the hydrocarbon slick and gelation of the spill that remains a key challenge in environmental oil-spill remediation with LMWOs. The application of the LMWO to the oil has proven to be highly exacting simply due to the strength of the gelling intermolecular forces, and a successful LMWO will most commonly manifest itself as a solid. Therefore, in order to solubilise a solid LMWO in oil, energy (heat) has to be applied to the system to overcome these intermolecular forces and force dissolution. On mixing with the oil and cooling, the intermolecular forces can re-form and the oil will gel.This is a severe limitation of LMWOs in the oil-spill clean-up role, as they must either: (a) be applied hot, increasing deployment difficulty and energetic cost or (b) to hasten dissolution in oil, they would have to be deployed in a carrier solvent, increasing potential environmental consequences. Potentially, this is also a reason why LMWOs would only be suited to inshore clean-up as the cooling on aerial deployment would mean the LMWO would solidify before reaching the oil, preventing dissolution and gelation.Several groups have published investigations along these lines, such as: using heated solutions of LMWOs,5,6 or supergelators dissolved in flammable ethanol/ethyl acetate blends of solvents to aid gel dissolution.7–9 Sureshan et al. reported alkyl 4,6-O-benzylidene-glucopyranoside derivatives which can be applied as a powder and will gel oil mixtures on seawater5 and more recently, Zhang et al. reported d-gluconic acetal-based powder gelators able to gel oil slicks at room temperature.10Another emerging school of thought involved the combinatorial approach of LMWOs coupled with sorbents.11 For example, the use of a supergelator (definition: a critical gelation concentration (CGC) of <0.1 wt%)12 contained within a cellulose pulp matrix has been shown to be very effective at absorbing oil and affecting the release of the gelator into the oil.13 This approach alleviates the need for a carrier solvent and solves the problem of dissolution, but does require the presence of a solid matrix to work.In an alternative solution to the aforementioned challenges, we utilised the rapid reaction of isocyanate and amine to form a LMWO in situ, a method first utilised by Suzuki et al., who used the in situ synthesis of urea-based LMWOs to gel a variety of solvents in 2004. Here we extend the method to oil-on-sea water slicks.14 We also explore for the first time, the influence of temperature on in situ gelation, going below room temperature to more accurately simulate oceanic conditions. Herein we can report the successful, rapid gelation of 1-octadecene using compound 1 as a slick on cold seawater (−5 °C), an experiment essential for validating this method in cold environments.If two liquid precursors, such as diisopropylamine and p-tolyl isocyanate were sprayed into an oil in close proximity or one after another, a gel can form in the oil in situ, thus alleviating the need for elevated temperature or a carrier solvent. We examined this hypothesis by simulating an oil slick utilising 1-octadecene on deionised water, before rapid injection of equimolar amounts of p-tolyl isocyanate and amine (diisopropylamine (forming N′-(4-methylphenyl)-N,N-dipropan-2-ylurea), henceforth referred to as compound 1 or dodecylamine (forming N-dodecyl-N′-(4-methylphenyl)-urea), henceforth referred to as compound 2). On injection, either the isocyanate after the amine or vice versa (or indeed simultaneously), urea fibres began to form rapidly, completely gelling the 1-octadecene within 60 seconds (Fig. 2, ,33 and ESI Video†), even on slicks at low temperature on seawater at −5 °C (see Fig. S2†). Rapid gelation within 60 seconds occurred with LMWO concentrations down to 2 wt% with the diisopropylamine/p-tolyl isocyanate system (1), and 5 wt% dodecylamine/p-tolyl isocyanate system (2), below which the reaction was slower with weaker gel consistency, and did not survive the “inversion test” (Fig. S1†). We successfully managed to form an LMWO in situ in an oil on water slick, through rapid reaction of isocyanate and amine precursors, as shown by nuclear magnetic resonance (NMR) spectroscopy in the ESI.† Indeed, water should compete for reaction with the isocyanate, but the localised high concentration precluded this. The NMR of the resulting gels did not show evidence of the isocyanate reaction with water in the oil slick, and no sequestered water in the oil. The resultant ureas and gelators were isolable from oil and could be extracted by distillation or centrifugation, as demonstrated in our previous work.4 We successfully repeated these experiments with kerosene and motor oil and several other oils at −5 °C (details in Table S1 ESI†).Open in a separate windowFig. 2Scanning electron microscope images of xerogels of: (a) and (b) 10 wt% diisopropylamine/p-tolyl isocyanate system (compound 1), and (c) and (d) 10 wt% dodecylamine/p-tolyl isocyanate system (compound 2).Open in a separate windowFig. 3Photographs demonstrating the experimental protocol. (a) is gelator 1, the product from the reaction p-tolyl isocyanate with diisopropylamine, (b), (d) and (f) show the process of simultaneous injection of p-tolyl isocyanate and diisopropylamine into a 1-octadecene on water slick forming a gel in (f), (c) a 100 ml round bottom flask filled with water held back by a 1/1-octadecene gel and (e) illustrates complete separation of a 1/1-octadecene gel and water.The selected “cores” and “tails” are low molecular weight, with neither exceeding 320 g mol−1. Precursors are all inexpensive (p-tolyl isocyanate is a poly(urethane) precursor) and alkyl amines which are readily available and inexpensive. The synthesis of ureas/carbamate from isocyanates and primary amines/alcohols is an instantaneous, facile one-pot reaction giving a pure product in high yield.4 Purification involved removal of the solvent (if any) and drying in vacuo. The process can easily be adapted to the kilogram scale, with prima facae evidence being the poly(urethane) industry. The LMWOs formed by this reaction are of unknown toxicity, but neither exhibited significant solubility in water, so are unlikely to pose a long-term threat to aquatic life.The in situ reaction was also very effective at gelling thin oil slicks (ca. 2 mm) and facilitated the collection of oil as evidenced in Fig. S3† and and3e3e respectively. SEM images in Fig. 2 (xerogels of dodecylamine/p-tolyl isocyanate and diisopropylamine/p-tolyl isocyanate formed from gelling cyclohexane) demonstrate the formation of urea “tapes” in the same fashion as our previous work.4 The dodecylamine/p-tolyl isocyanate gel however formed more plate-like structures (Fig. 2(c) and (d)).The rapidity of reaction is very important for deployment of the in situ method system for fast clean-up of oil spills. Indeed, the use of diisopropylamine over dodecylamine facilitates a more rapid reaction, as evidenced by Video S2 in the ESI.† We postulate that this is simply due to the small size of the diisopropylamine versus the dodecylamine, with the smaller diisopropylamine being able to react faster. Further to this, pump oil on river water (obtained from the River Thames near Kingston) was gelled successfully with both the dodecylamine/p-tolyl isocyanate and diisopropylamine/p-tolyl isocyanate systems. In terms of concentrations of precursors applied, we were able to invert 1 ml of 1-octadecene gels formed with the precursors applied against 2 ml of deionised water (see Fig. S4†). The integrity of gels of 1 was maintained down to 1 wt%, whereas for 2, integrity was maintained down to 2 wt% of gelator.NMR spectroscopy confirmed that both gelators 1 and 2 were formed in high yield on reaction of p-tolyl isocyanate and diisopropylamine/dodecylamine respectively, in the absence of solvent (ESI†). Furthermore, the same reagents reacted together successfully and in quantitative yields when added separately or together to a 1-octadecene layer on an aqueous layer. The gel formed in those cases dissolved fully in CDCl3 with no significant amount of water present in the gel. This seemed to indicate no sequestration of water by the gel as it formed.One of the main problems with the approach outlined herein is toxicity. The safety datasheets (SDS) for both diisopropylamine and p-tolylisocyanate class them as irritants and as toxic. In order to ascertain the amount of precursors and gelator that leached into the aqueous phase, various slicks of 1-octadecene were created on seawater and river water before injection of precursors into the oil layer. The aqueous phases were then analysed for leachates by NMR. The results are summarised in Table 1.Amounts of leachates (p-tolylamine, diisopropylamine, dodecylamine, gelator) found in aqueous layers
Open in a separate windowaHydrolysis product of p-tolylisocyanate, internal standard was dimethylsulfone, δH (D2O) = 3.15 ppm (internal reference TSP), ND = not detectable above noise level.bSample from 2% wt/wt gelator : oil ratio (i.e. 2 tenths of previous sample). The values reported above are those determined from a single NMR sample on one peak for each analyte where a signal to noise ratio (S/N) above 240 was measured (unless otherwise noted). When other peaks were available for integration which had S/N in as low as 77 the resulting concentrations were essentially the same as those presented above.The leaching experiments seem to indicate very little dodecylamine or its gelator compound 2 leached from the oil (1-octadecene) to the aqueous layer. However, a trace amount of diisopropylamine was detected by 1H NMR in the case of 1, as was p-tolylamine the by-product resulting from the hydrolysis of isocyanate. These findings indicate that the long alkyl chain in dodecylamine and 2 prevent appreciable leaching into aqueous media. The leaching of p-tolylisocyanate was consistent in both river and seawater. This led the investigators to conclude that if a more hydrophobic isocyanate was used as a LMWO precursor in conjunction with dodecylamine, then leaching could be prevented altogether. Therefore, we have largely overcome the toxicity hazards associated with the in situ delivery method, paving the way for similar in situ generation of LMWO molecules from reactive precursors in future. We note that recent advances in “green isocyanate” synthesis from renewable feedstocks may also reduce environmental concerns of our method.15,16 相似文献
| Leaching experiment | Respective leachate (parts per million) | |||
|---|---|---|---|---|
| p-Tolylaminea | Diisopropyl-amine | Dodecylamine | Gelator | |
| 1 on sea water | 30 | 27 (S/N = 58) | — | 50 |
| 1 on river water | 35 | 28 | — | 61 |
| 1 2% on river waterb | 33 | 51 | — | 40 |
| 2 on sea water | 26 | — | ND | ND |
| 2 on river water | 27 | — | ND | ND |
996.
Stefano Montelli Jean-Marie Graïc Jaime Antonio Ruiz Calogero Stelletta Antonella Peruffo 《Anatomical record (Hoboken, N.J. : 2007)》2020,303(11):2865-2877
In this study we performed a neurochemical characterization of the hypothalamus in the developing alpaca (Vicugna pacos) with the aim of revealing the distributions of immunoreactive (-ir) cells containing parvalbumin (PV), calbindin (CB), calretinin (CR), the somatostatin (SOM), the enzyme aromatase P450 (P450Arom), the estrogen receptor α (ER-α), and estrogen receptor β (ER-β) in embryonal stages, early fetal age, and in the newborn. This analysis has been carried out on embryos at 20, 30, 45 days, fetuses at 90 days, and newborn alpaca. Our immunohistochemical results revealed no cells-ir throughout the embryonic hypothalami of 20, 30, and 45 days. On the fetal stage of 90 days, SOM-ir cells were observed in the lateral hypothalamus and the ventromedial nuclei of the tuberal region. We checked for the presence of P450Arom-ir cells in the periventricular area and dorsomedial hypothalamic nucleus of the tuberal region. In these fetal stages, no PV-ir, CB-ir, CR-ir or ERs-ir cells were identified. In the newborn, the PV-ir, CB-ir, CR-ir, and SOM-ir cells were detected in both the anterior and tuberal hypothalamic area. The P450Arom-ir cells the ER-α–ir and ER-β–ir cells were found in the anterior hypothalamus. Our results offer a contribution in the future purpose to obtain a time-expression pattern of the considered markers in alpaca during gestation and represents a foundation for future investigations on the alpaca brain to define the cross talk between PV, CB, CR, P450Arom, SOM, and ERs in the hypothalamus, the strategic region for the control of the reproductive behavior. 相似文献
997.
Minal R. Patel Peter X. K. Song Jean-Marie Bruzzese Wei Hao David Evans Lara J. Thomas 《The Journal of asthma》2019,56(3):273-284
Objective: Adverse cross-cultural interactions are a persistent problem within medicine impacting minority patients' use of services and health outcomes. To test whether 1) enhancing the evidence-based Physician Asthma Care Education (PACE), a continuing medical education program, with cross cultural communication training (PACE Plus) would improve the asthma outcomes of African American and Latino/Hispanic children; and 2) whether PACE is effective in diverse groups of children. Methods: A three-arm randomized control trial was used to compare PACE Plus, PACE, and usual care. Participants were primary care physicians (n = 112) and their African American or Latino/Hispanic pediatric patients with persistent asthma (n = 867). The primary outcome of interest included changes in emergency department visits for asthma overtime, measured at baseline, and 9 and 21 months following the intervention. Other outcomes included hospitalizations, asthma symptom experience, caregiver asthma-related quality of life, and patient-provider communication measures. Results: Over the long term, PACE Plus physicians reported significant improvements in confidence and use of patient-centered communication and counseling techniques (p < 0.01) compared to PACE physicians. No other significant benefit in primary and secondary outcomes was observed in this trial. Conclusion: PACE Plus did not show significant benefit in asthma-specific clinical outcomes. More trials and multi-component strategies continue to be needed to address complex risk factors and reduce disparities in asthma care.
Trial registration: ClinicalTrials.gov: NCT01251523 December 1, 2010. 相似文献
998.
Nicolas Tarbouriech Florian Chenavier Junna Kawasaki Kamel Bachiri Jean-Marie Bourhis Pierre Legrand Lily L. Freslon Estelle M. N. Laurent Elsa Suberbielle Rob W. H. Ruigrok Keizo Tomonaga Daniel Gonzalez-Dunia Masayuki Horie Etienne Coyaud Thibaut Crpin 《Viruses》2022,14(11)
Determining the structural organisation of viral replication complexes and unravelling the impact of infection on cellular homeostasis represent important challenges in virology. This may prove particularly useful when confronted with viruses that pose a significant threat to human health, that appear unique within their family, or for which knowledge is scarce. Among Mononegavirales, bornaviruses (family Bornaviridae) stand out due to their compact genomes and their nuclear localisation for replication. The recent recognition of the zoonotic potential of several orthobornaviruses has sparked a surge of interest in improving our knowledge on this viral family. In this work, we provide a complete analysis of the structural organisation of Borna disease virus 1 (BoDV-1) phosphoprotein (P), an important cofactor for polymerase activity. Using X-ray diffusion and diffraction experiments, we revealed that BoDV-1 P adopts a long coiled-coil α-helical structure split into two parts by an original β-strand twist motif, which is highly conserved across the members of whole Orthobornavirus genus and may regulate viral replication. In parallel, we used BioID to determine the proximal interactome of P in living cells. We confirmed previously known interactors and identified novel proteins linked to several biological processes such as DNA repair or mRNA metabolism. Altogether, our study provides important structure/function cues, which may improve our understanding of BoDV-1 pathogenesis. 相似文献
999.
Yi Wang Handong Xu Can Hu Pengcheng Yu Zhehan Bao Yanqiang Zhang Ruolan Zhang Shengjie Zhang Bing Li Jean-Marie Aerts Zhiyuan Xu Xiangdong Cheng 《Journal of gastrointestinal oncology.》2022,13(3):1046
BackgroundNeoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC.MethodsIn total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients.ResultsAmong the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients.ConclusionsTRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response. 相似文献
1000.
Daniel Tran Tiffanie Girault Marjorie Guichard Sbastien Thomine Nathalie Leblanc-Fournier Bruno Moulia Emmanuel de Langre Jean-Marc Allain Jean-Marie Frachisse 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(1)
Plants spend most of their life oscillating around 1–3 Hz due to the effect of the wind. Therefore, stems and foliage experience repetitive mechanical stresses through these passive movements. However, the mechanism of the cellular perception and transduction of such recurring mechanical signals remains an open question. Multimeric protein complexes forming mechanosensitive (MS) channels embedded in the membrane provide an efficient system to rapidly convert mechanical tension into an electrical signal. So far, studies have mostly focused on nonoscillatory stretching of these channels. Here, we show that the plasma-membrane MS channel MscS-LIKE 10 (MSL10) from the model plant Arabidopsis thaliana responds to pulsed membrane stretching with rapid activation and relaxation kinetics in the range of 1 s. Under sinusoidal membrane stretching MSL10 presents a greater activity than under static stimulation. We observed this amplification mostly in the range of 0.3–3 Hz. Above these frequencies the channel activity is very close to that under static conditions. With a localization in aerial organs naturally submitted to wind-driven oscillations, our results suggest that the MS channel MSL10, and by extension MS channels sharing similar properties, represents a molecular component allowing the perception of oscillatory mechanical stimulations by plants.Throughout their life, plants are submitted to recurrent cyclic mechanical loading due to wind. The resulting passive oscillation movements of stems and foliage are an important phenomenon for biological and ecological processes such as photosynthesis (1–3) and thermal exchange (4). The motions induced are well described and analyzed at the whole plant scale, with oscillations at typically 1–3 Hz in trees (5–10). In animals, transduction of vibrational stimulation is achieved through mechanosensitive (MS) channels in organs with specialized structures, such as the ear in which the different frequencies are spatially separated (11), or as in touch perception accomplished through organ motion (12). In plants, such specialized features have not yet been reported, and it remains unclear whether and how MS channels participate in the perception of oscillatory stimuli. To investigate this question, we studied MscS-LIKE 10 (MSL10) family members, homologs of the Mechanosensitive channel of Small conductance (MscS) from Escherichia coli (13–15), as they are found in all land plant genomes (16). We have focused our study on the plasma-membrane-localized MSL10 (17, 18). 相似文献
