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Astroglia play an important role, providing de novo synthesized cholesterol to neurons in the form of ApoE-lipidated particles; disruption of this process can increase the risk of Alzheimer’s disease. We recently reported that glia-specific suppression of the lipolysis-stimulated lipoprotein receptor (LSR) gene leads to Alzheimer’s disease-like memory deficits. Since LSR is an Apo-E lipoprotein receptor, our objective of this study was to determine the effect of LSR expression modulation on cholesterol and ApoE output in mouse astrocytes expressing human ApoE3. qPCR analysis showed that siRNA-mediated lsr knockdown significantly increased expression of the genes involved in cholesterol synthesis, secretion, and metabolism. Analysis of media and lipoprotein fractions showed increased cholesterol and lipidated ApoE output in HDL-like particles. Further, lsr expression could be upregulated when astrocytes were incubated 5 days in media containing high levels (two-fold) of lipoprotein, or after 8 h treatment with 1 µM LXR agonist T0901317 in lipoprotein-deficient media. In both conditions of increased lsr expression, the ApoE output was repressed or unchanged despite increased abca1 mRNA levels and cholesterol production. We conclude that LSR acts as a sensor of lipoprotein content in the medium and repressor of ApoE release, while ABCA1 drives cholesterol efflux, thereby potentially affecting cholesterol load, ApoE lipidation, and limiting cholesterol trafficking towards the neuron.  相似文献   
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The complete mitochondrial DNA sequence of the Nursehound Scyliorhinus stellaris has been determined for the first time and compared with congeneric species. The mitogenome sequence was 16,684 bp in length. The mitogenome is composed of 13 PCGs, 2 rRNAs, 22 transfer RNA genes and non-coding regions. The gene order of the newly sequenced mitogenome is analogous to the organization described in other vertebrate genomes. The typical conservative blocks in the control region were indicated. The phylogenetic analysis revealed a monophyletic origin of the Scyliorhininae subfamily, and within it, two subclades were identified. A significant divergence of Scyliorhinus spp. together with Poroderna patherinum in relation to the group of Cephaloscyllium spp. was observed, except for Scyliorhinus torazame, more related to this last cited clade. A hypothesis of a divergent evolution consequent to a selective pressure in different geographic areas, which lead to a global latitudinal diversity gradient, has been suggested to explain this phylogenetic reconstruction. However, convergent evolution on mitochondrial genes could also involve different species in some areas of the world.  相似文献   
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The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).  相似文献   
135.
    
Parkinson’s disease is one of the most common neurodegenerative disorders worldwide, characterized by a progressive loss of dopaminergic neurons mainly localized in the substantia nigra pars compacta. In recent years, the detailed analyses of both genetic and idiopathic forms of the disease have led to a better understanding of the molecular and cellular pathways involved in PD, pointing to the centrality of mitochondrial dysfunctions in the pathogenic process. Failure of mitochondrial quality control is now considered a hallmark of the disease. The peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) family acts as a master regulator of mitochondrial biogenesis. Therefore, keeping PGC-1 level in a proper range is fundamental to guarantee functional neurons. Here we review the major findings that tightly bond PD and PGC-1s, raising important points that might lead to future investigations.  相似文献   
136.
    
BACKGROUND: The design of polymeric vectors for gene delivery provided with specific properties is one of the most critical aspects for a successful gene therapy. These polymers should be biocompatible as well as able to carry efficiently DNA to target tissues and to transfect it into cells. RESULTS: The formation of complexes of poly[(α,β‐asparthylhydrazide)–poly(ethylene glycol)] and poly[(α,β‐asparthylhydrazide)–hexadecylamine] copolymers functionalised with glycidyltrimethylammonium chloride (PAHy–PEG‐GTA and PAHy–C16‐GTA, respectively) with DNA was studied. The effects of the introduction of hydrophilic (PEG) or hydrophobic (C16) moieties on the chains of PAHy–GTA copolymers, such as the stabilising effect on the DNA structure, were evaluated. In particular, we observed a high DNA protection by PAHy–PEG‐GTA copolymers. Degradation studies led us to suppose a particular aqueous conformation of the polyionic complex of PAHy–PEG2000‐GTA in which DNA should be internalised into an inner core surrounded by a PEG hydrophilic shell; while no significant protection was detected with PAHy–C16‐GTA in which DNA should be disposed on the surface of the complex, freely exposed to DNase II action. CONCLUSION: The insertion of PEG or C16 chains into the polymeric structure of PAHy–GTA copolymers changes significantly the DNA complexing and protecting ability of the PAHy–GTA copolymers, showing that hydrophilic and hydrophobic side chains can play a crucial role in supramolecular arrangements of interpolyelectrolyte complexes between DNA and PAHy copolymers. Copyright © 2008 Society of Chemical Industry  相似文献   
137.
    
The water solutions of the block copolymers PEOn‐PPOm‐PEOn, known as pluronics, show a complex thermal behavior, since they are liquid at low temperature (5°C), and they can give soft gel when heated at body temperature (37°C). These properties are of great interest in biomedical applications. To properly design these applications, a prerequisite is the knowledge of the thermodynamics—how much—and of the kinetics—how fast—with which these transformations take place. In this work, solutions of F127 (the copolymer for which n = 100 and m = 65) were studied by varying the concentration and the temperature and analyzing their behavior when heated under several heating rates. The studies were performed by differential scanning calorimetry (DCS) and dielectric spectroscopy. The investigations carried out under equilibrium conditions allowed us to determine the thermodynamics of the phase transitions, whereas the investigations carried out under varying conditions allowed us to quantify the kinetics of the phase transitions. Empirical models were also proposed to describe both the thermodynamics and the kinetics observed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009  相似文献   
138.
    
During the last decade, on-surface fabricated graphene nanoribbons (GNRs) have gathered enormous attention due to their semiconducting π-conjugated nature and atomically precise structure. A significant breakthrough is the recent fabrication of nanoporous graphene (NPG) as a 2D array of laterally bonded GNRs. This covalent integration of GNRs could enable complex electronic functionality at the nanoscale; however, for that, it is crucial to externally control the electronic coupling between GNRs within NPGs, which, to date, has not been possible. Using quantum chemical calculations and large-scale transport simulations, this study demonstrates that such control is enabled in a newly designed quinone-NPG (q-NPG) thanks to its GNRs inter-connections based on electroactive para-benzoquinone units. As a result, the spatial distribution of injected currents in q-NPG may be tuned, with sub-nanometer precision, via the application of external electrostatic gates and electrochemical means. These results thus provide a fundamental strategy to design organic nanodevices with built-in externally tunable electronics and spintronics, which is key for future applications such as bio-chemical nanosensing and carbon nanoelectronics.  相似文献   
139.
    
Introduction: During hemodialysis (HD) the interaction of the blood with the dialyzer triggers both an inflammatory reaction and an activation of the coagulation cascade. An accepted parameter to quantify the extent of coagulation activation during HD is not available. This study aims to evaluate its amplitude, comparing dialyzers made of different polysulfone polymers, by measuring D‐dimers in the filter‐rinsing fluids (Frf) and to test whether Frf D‐dimers are suitable candidate markers to assess contact coagulation activation during HD. Methods: In a prospective, cross‐over study 41 hemodialysis patients were randomly allocated to nine HD sessions with three types of polysulfone membranes: Filter A: Poliflux®RevaclearMAX; Filter B: Helixone®Fx80, Filter C: Polyflux®H210. Findings: A total of 117 HD sessions were studied. The mean (SD) filter (Frf) D‐dimers were 0.19 µg/L (0.56) for Filter A; 0.66 µg/L (2.81) for Filter B; 0.33 µg/L (1.13) for Filter C. Significant differences were found: A vs. B (P < 0.01), A vs. C (P = 0.01); B vs. C not significant. A large between‐patient variability of D‐dimer filter levels was found. D‐Dimers in blood showed a similar trend but differences were not significant. Discussion: The contact activation of coagulation during HD may also vary among filters made up with similar polysulfones. D‐dimer in the filter rinsing fluid but not in the blood can be considered a candidate marker for the evaluation of thrombogenicity during HD. Further studies are needed to elucidate the mechanism(s) and to confirm the usefulness of filter rinsing fluid D‐Dimers as a clotting activation marker during HD.  相似文献   
140.
最新国内和国际的抗震规范对既有建筑和新设计结构抗震评估之间的差异进行了论述。发布了材料结构特征的详细指南,以及完成可靠性分析的特有程序。光面钢筋混凝土结构的抗震性能模型具有重要作用,需要进一步完善。对钢筋混凝土柱的试验结果进行了报道,这些钢筋混凝土柱按照老规范设计,可追溯到20世纪40-70年代。研究聚焦在单调荷载下构件的转动能力以及对两个文献中拓展研究报告的第一部分进行描述,两个文献均对单调和循环问题进行研究。  相似文献   
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