全文获取类型
收费全文 | 2209篇 |
免费 | 131篇 |
国内免费 | 11篇 |
学科分类
医药卫生 | 2351篇 |
出版年
2023年 | 16篇 |
2022年 | 34篇 |
2021年 | 54篇 |
2020年 | 39篇 |
2019年 | 41篇 |
2018年 | 64篇 |
2017年 | 53篇 |
2016年 | 60篇 |
2015年 | 61篇 |
2014年 | 87篇 |
2013年 | 83篇 |
2012年 | 155篇 |
2011年 | 162篇 |
2010年 | 86篇 |
2009年 | 84篇 |
2008年 | 113篇 |
2007年 | 137篇 |
2006年 | 171篇 |
2005年 | 111篇 |
2004年 | 130篇 |
2003年 | 108篇 |
2002年 | 112篇 |
2001年 | 32篇 |
2000年 | 29篇 |
1999年 | 41篇 |
1998年 | 22篇 |
1997年 | 17篇 |
1996年 | 25篇 |
1995年 | 10篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1992年 | 17篇 |
1991年 | 19篇 |
1990年 | 15篇 |
1989年 | 12篇 |
1988年 | 18篇 |
1987年 | 4篇 |
1986年 | 9篇 |
1985年 | 11篇 |
1984年 | 8篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1977年 | 4篇 |
1975年 | 4篇 |
1974年 | 7篇 |
1971年 | 7篇 |
1970年 | 12篇 |
1966年 | 4篇 |
排序方式: 共有2351条查询结果,搜索用时 15 毫秒
71.
72.
Conserved and divergent expression patterns of markers of axial development in the laboratory opossum,Monodelphis domestica 下载免费PDF全文
Michio Yoshida Eriko Kajikawa Daisuke Yamamoto Daisuke Kurokawa Shigenobu Yonemura Kensaku Kobayashi Hiroshi Kiyonari Shinichi Aizawa 《Developmental dynamics》2016,245(12):1176-1188
Background: Previous comparative studies suggest that the requirement for Nodal in epiblast and hypoblast development is unique to mammalians. Expression of anterior visceral endoderm (AVE) genes in the visceral endoderm and of their orthologs in the hypoblast may be unique to mammalians and avians, and is absent in the reptilian hypoblast. Axis formation in reptiles is signaled by the formation of the posterior marginal epiblast (PME), which expresses a series of primitive streak genes. To assess the phylogenetic origin of Nodal and AVE gene expression and axis formation in amniotes, we examined marker gene expression in gray short‐tailed opossum, a metatherian. Results: Nodal was expressed in neither epiblast nor hypoblast of opossum embryos. No AVE genes were expressed in the opossum hypoblast. Attainment of polarity in the embryonic disk was signaled by Nodal, Wnt3a, Fgf8, and Bra expression in the PME at 8.5 days post‐coitus. Conclusions: Nodal expression in epiblast or hypoblast may be unique to eutherians. AVE gene expression in visceral endoderm and hypoblast may have been independently acquired in eutherian and avian lineages. PME formation appears to be the event that signals axis formation in reptilian and metatherian embryos, and thus may be an ancestral characteristic of basal amniotes. Developmental Dynamics 245:1176–1188, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
73.
Eriko Anzai RN MN Clint Douglas RN PhD Ann Bonner RN PhD 《Nursing & health sciences》2014,16(2):171-178
The purpose of this study was to describe Japanese hospital nurses' perceptions of the nursing practice environment and examine its association with nurse‐reported ability to provide quality nursing care, quality of patient care, and ward morale. A cross‐sectional survey design was used including 223 nurses working in 12 acute inpatient wards in a large Japanese teaching hospital. Nurses rated their work environment favorably overall using the Japanese version of the Practice Environment Scale of the Nursing Work Index. Subscale scores indicated high perceptions of physician relations and quality of nursing management, but lower scores for staffing and resources. Ward nurse managers generally rated the practice environment more positively than staff nurses except for staffing and resources. Regression analyses found the practice environment was a significant predictor of quality of patient care and ward morale, whereas perceived ability to provide quality nursing care was most strongly associated with years of clinical experience. These findings support interventions to improve the nursing practice environment, particularly staffing and resource adequacy, to enhance quality of care and ward morale in Japan. 相似文献
74.
Nobutsugu Abe Masanori Sugiyama Yutaka Suzuki Osamu Yanagida Tadahiko Masaki Toshiyuki Mori Yutaka Atomi 《Journal of Hepato-Biliary-Pancreatic Surgery》2009,16(2):184-188
Background/purpose Pancreatic fistula, which is one of the main causes of late postpancreatectomy hemorrhage (PPH), is a common complication
of pancreatoduodenectomy (PD). It may erode the anastomosis site and vascular wall in its vicinity, resulting in pseudoaneurysm
formation and/or the rupture of major vessels. To protect the vessels near the area for pancreaticojejunostomy from potential
pancreatic fistula, we have adopted a surgical option by which such vessels are separated from the pancreaticojejunostomy
using a pedicled falciform ligament. We reviewed 36 patients who underwent PD that included this option.
Methods After the PD was completed (before reconstructions), the pedicled falciform ligament was spread widely on the major vessels
exposed during resection, and was fixed to the surrounding retroperitoneal connective tissue. These procedures enabled the
complete separation of these vessels from the pancreaticojejunostomy.
Results The mobilization and placement of the falciform ligament in the space between the pancreaticojejunostomy and the major vessels
were successfully carried out without any complications. Although ten (28%) patients developed pancreatic fistula and three
(8%) developed intraabdominal infection, none of the patients developed late PPH.
Conclusions The present surgical option is technically simple and easy, and may be an effective prophylactic measure against late PPH
following PD. 相似文献
75.
76.
Akitoshi Hakoda Toshihisa Takeuchi Yuichi Kojima Yasuhiro Fujiwara Yasuaki Nagami Yuji Naito Shinsaku Fukuda Tomoyuki Koike Mitsushige Sugimoto Kenta Hamada Hideki Kobara Norimasa Yoshida Tomoki Inaba Akihito Nagahara Eriko Koizumi Kazunari Murakami Takahisa Furuta Naotaka Ogasawara Hajime Isomoto Kotaro Shibagaki Hiromi Kataoka Hidekazu Suzuki Kazuhide Higuchi 《Journal of Clinical Biochemistry and Nutrition》2022,70(2):189
Bleeding after gastric endoscopic submucosal dissection (ESD) remains problematic, especially in patients receiving antithrombotic therapy. Therefore, this study aimed to identify the risk factors. In this retrospective study, patients (n = 1,207) who underwent gastric ESD while receiving antithrombotic therapy were enrolled at Osaka Medical and Pharmaceutical University Hospital and 18 other referral hospitals in Japan. Risks of post-ESD bleeding were calculated using multivariable logistic regression. The dataset was divided into a derivation cohort and a validation cohort. We created a prediction model using the derivation cohort. The accuracy of the model was evaluated using the validation cohort. Post-ESD bleeding occurred in 142 (11.8%) participants. Multivariable analysis yielded an odds ratio of 2.33 for aspirin, 4.90 for P2Y12 receptor antagonist, 1.79 for cilostazol, 0.95 for other antithrombotic agents, 6.53 for warfarin, 5.65 for dabigatran, 7.84 for apixaban, 10.45 for edoxaban, 6.02 for rivaroxaban, and 1.46 for heparin bridging. The created prediction model was called safe ESD management using the risk analysis of post-bleeding in patients with antithrombotic therapy (SAMURAI). This model had good predictability, with a C-statistic of 0.77. In conclusion, use of the SAMURAI model will allow proactive management of post-ESD bleeding risk in patients receiving antithrombotic therapy. 相似文献
77.
Negishi J Kawanami M Terada Y Matsuhashi C Ogami E Iwasaka K Hongo T 《Journal of the International Academy of Periodontology》2004,6(4):120-124
Lifestyle and socioeconomic status have been associated with the disease status of diabetic patients. However, there have been few reports on the relationship between these factors and the periodontal condition of diabetics. We assessed the association between disease status and lifestyle of diabetic patients and clinical features of advanced periodontitis such as deep probing depths and severe alveolar bone loss. Fifty-seven diabetic patients were examined in this study. Clinical assessment of probing pocket depth and radiographic alveolar bone loss was performed. Data regarding diabetic status and lifestyle of the diabetic patients were also recorded and statistically analysed by logistic regression. Drinking habits and high values of hemoglobin A1c (HbA1c) (>9.0%) were significantly associated with deep probing depth. The odds ratios (OR) of these factors were 7.72 (95% confidence interval (CI), 1.80 to 33.19), and 6.10 (95% CI = 1.23 to 30.25), respectively. Presence of complications such as retinopathy (OR = 8.86, 95% CI, 1.99 to 39.40), irascible behaviour (OR = 8.40, 95% CI = 1.33 to 53.17) and high value of HbA1c (OR = 4.94, 95% CI = 1.14 to 21.46) were significantly related to mean advanced alveolar bone loss. Only the high value of HbA1c (OR = 3.53, 95% CI = 1.06 to 11.73) was detected as a significant factor related to advanced periodontitis, characterised by more than 50% mean alveolar bone loss, or two or more teeth with probing depth greater than 6 mm. In conclusion, drinking habit and irascible behaviour are correlated with the periodontal disease condition of diabetic patients, in addition to a high value of HbA1c (>9.0%). Lifestyle and psychosocial stress may affect the periodontal disease status of diabetic patients. 相似文献
78.
79.
Yasushi Yamasaki Keita Harada Shumpei Yamamoto Eriko Yasutomi Shotaro Okanoue Mami Hirai Shohei Oka Yuka Obayashi Hiroyuki Sakae Kenta Hamada Toshihiro Inokuchi Hideaki Kinugasa Yuusaku Sugihara Masahiro Takahara Takehiro Tanaka Sakiko Hiraoka Yoshiro Kawahara Hiroyuki Okada 《Digestive endoscopy》2020,32(5):791-800
80.
Toshiaki Hosaka Takashi Nomura Minoru Kubo Takanori Nakane Luo Fangjia Shun-ichi Sekine Takuhiro Ito Kazutaka Murayama Kentaro Ihara Haruhiko Ehara Kazuhiro Kashiwagi Kazushige Katsura Ryogo Akasaka Tamao Hisano Tomoyuki Tanaka Rie Tanaka Toshi Arima Ayumi Yamashita Michihiro Sugahara Hisashi Naitow Yoshinori Matsuura Susumu Yoshizawa Kensuke Tono Shigeki Owada Osamu Nureki Tomomi Kimura-Someya So Iwata Eriko Nango Mikako Shirouzu 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(9)
Light-driven chloride-pumping rhodopsins actively transport anions, including various halide ions, across cell membranes. Recent studies using time-resolved serial femtosecond crystallography (TR-SFX) have uncovered the structural changes and ion transfer mechanisms in light-driven cation-pumping rhodopsins. However, the mechanism by which the conformational changes pump an anion to achieve unidirectional ion transport, from the extracellular side to the cytoplasmic side, in anion-pumping rhodopsins remains enigmatic. We have collected TR-SFX data of Nonlabens marinus rhodopsin-3 (NM-R3), derived from a marine flavobacterium, at 10-µs and 1-ms time points after photoexcitation. Our structural analysis reveals the conformational alterations during ion transfer and after ion release. Movements of the retinal chromophore initially displace a conserved tryptophan to the cytoplasmic side of NM-R3, accompanied by a slight shift of the halide ion bound to the retinal. After ion release, the inward movements of helix C and helix G and the lateral displacements of the retinal block access to the extracellular side of NM-R3. Anomalous signal data have also been obtained from NM-R3 crystals containing iodide ions. The anomalous density maps provide insight into the halide binding site for ion transfer in NM-R3.Microbial ion-pumping rhodopsins are integral membrane proteins that actively transport ions across membranes upon light stimulation (1). Bacteriorhodopsin (bR) and halorhodopsin (HR) are well-known microbial ion-pumping rhodopsins found in halophilic archaea (2, 3). bR is a light-driven outward proton pump and HR is a light-driven inward anion pump, specific for chloride ion. Microbial ion-pumping rhodopsins possess common structural features consisting of seven α-helices with an all-trans retinal covalently bound to a lysine residue as the chromophore, despite the transport of different ions (4). The retinal undergoes photoisomerization from the all-trans to 13-cis configuration, which initiates the photocycle accompanied by several intermediates to export ions (4, 5). Its light-controllable function is suitable for optogenetics applications for manipulating cells, such as neurons, by changing the ion concentration inside or outside the membrane (6, 7). In fact, microbial rhodopsins, including channelrhodopsins and HRs, are employed as optogenetic tools (8–10).Nonlabens marinus rhodopsin-3 (NM-R3) is a light-driven chloride pump recently discovered in a marine flavobacterium (11). It is a distinct chloride pump from HRs and shows low amino acid sequence homology with HRs (11). To date, HR-type chloride pumps have been found in haloarchaea, marine bacteria, and cyanobacteria, including Halobacterium salinarum, Natronomonas pharaonis, and Mastigocladopsins repens, with sequence identities of 20%, 21%, and 20% to NM-R3, respectively (3, 12–15). Interestingly, NM-R3 has higher sequence identity (36%) to Krokinobacter rhodopsin 2 (KR2), a sodium pump found in Krokinobacter eikastus (16). NM-R3 possesses a unique NTQ motif (Asn98, Thr102, Gln109) in the third helix (helix C), which corresponds to key residues (DTD motif, Asp85, Thr89, Asp96) for proton transport in bR (11, 17, 18) (SI Appendix, Table S1). Asp85 acts as the primary proton acceptor of bR from the protonated Schiff-base (PSB), with assistance from Thr89 and Asp96, which is the proton donor (5, 17, 18). HRs from haloarchaea have a highly conserved TSA (Thr, Ser, Ala) motif, while the Ala residue is replaced by Asp in HR from cyanobacteria (19). In the X-ray crystal structure of NM-R3 (SI Appendix, Fig. S1A), a chloride ion located between the PSB and Asn98 (SI Appendix, Fig. S1B) is stabilized by the positive charge of the PSB (20). The position of this chloride ion is similar to those in the H. salinarum HR and N. pharaonis HR (NpHR) structures except for Thr and Ser, which correspond to Asn98 and Thr102 in NM-R3, respectively (20–22). Several amino acid residues around the retinal, including Arg95, Trp99, Trp201, and Asp231, are highly conserved among ion-pumping rhodopsins. Previous spectroscopic studies suggested that NM-R3 displays a similar sequence of intermediates, with K-, L-, N-, and O-like species, as in other HRs (23) (Fig. 1A). Recently, intermediate structures of NM-R3 obtained by low-temperature trapping X-ray crystallography and serial femtosecond crystallography (SFX) have been reported (24, 25). However, the detailed ion-pump mechanism still remains unclear, due to the lack of dynamic structures of anion transport at atomic resolution.Open in a separate windowFig. 1.TR-visible absorption spectroscopy for microcrystals. (A) Photocycle model of NM-R3 in the 1 M NaCl buffer solution (23). (B) TR difference spectra ΔA upon the 532-nm excitation. The difference was calculated by subtracting the spectrum of NM-R3. (C) Global fitting analysis with two exponentials. The A1 and A2 amplitude spectra correspond to the differences of [ΔAO – ΔA10 µs] and [ΔA200 ms − ΔAO], respectively. Here, ΔAO represents the difference spectrum of the O intermediate minus NM-R3. (D) The isomeric forms of the retinal chromophore in bacterial-type rhodopsins.Time-resolved serial femtosecond crystallography (TR-SFX) is a powerful tool for visualizing reactions and motions in proteins at the atomic level (26–28). In SFX, myriads of microcrystals are continuously injected by a sample injector into an irradiation point of X-ray free electron lasers (XFELs) at room temperature, thus providing diffraction patterns before the onset of radiation damage by the intense X-ray pulse. Combined with a visible-light pump laser for reaction initiation, TR-SFX has been applied to light-driven ion pumps to observe the structural dynamics during the ion transfer. While TR-SFX has revealed femto-to-millisecond structural dynamics in light-driven cation pumps, including bR and KR2 (29–31), TR-SFX studies of anion pumps have been limited to early-stage structures adopted at picoseconds after light illumination (32). In addition, although NM-R3 pumps a chloride ion (Cl−) as a physiological substrate, it can also transport bromide (Br−), iodide (I−), and other anions from the extracellular side to the cytoplasmic side (23). I− or Br− serves as a marker for tracking the positions of ions, due to the greater number of electrons, whereas Cl− is less distinguishable in X-ray crystallography. Therefore, TR-SFX experiments using I− or Br− are expected to directly visualize the process of ion transport.Here, we report the conformational alterations in NM-R3 during Br− or I− pumping, obtained by both TR-SFX and time-resolved spectroscopy of crystals. The resulting sequence of movements in NM-R3 demonstrates how the chloride pump transports anions with a large ionic radius and prevents the backflow of anions from the cytoplasmic side. 相似文献