全文获取类型
收费全文 | 41826篇 |
免费 | 3038篇 |
国内免费 | 544篇 |
出版年
2023年 | 239篇 |
2022年 | 412篇 |
2021年 | 727篇 |
2020年 | 582篇 |
2019年 | 678篇 |
2018年 | 996篇 |
2017年 | 857篇 |
2016年 | 1296篇 |
2015年 | 1974篇 |
2014年 | 2003篇 |
2013年 | 2746篇 |
2012年 | 3224篇 |
2011年 | 3003篇 |
2010年 | 1813篇 |
2009年 | 1545篇 |
2008年 | 2407篇 |
2007年 | 2317篇 |
2006年 | 2169篇 |
2005年 | 1986篇 |
2004年 | 1817篇 |
2003年 | 1660篇 |
2002年 | 1550篇 |
2001年 | 817篇 |
2000年 | 763篇 |
1999年 | 695篇 |
1998年 | 353篇 |
1997年 | 306篇 |
1996年 | 282篇 |
1995年 | 277篇 |
1994年 | 250篇 |
1993年 | 220篇 |
1992年 | 410篇 |
1991年 | 375篇 |
1990年 | 353篇 |
1989年 | 314篇 |
1988年 | 307篇 |
1987年 | 246篇 |
1986年 | 256篇 |
1985年 | 246篇 |
1984年 | 175篇 |
1983年 | 166篇 |
1982年 | 142篇 |
1981年 | 168篇 |
1979年 | 201篇 |
1978年 | 169篇 |
1977年 | 140篇 |
1976年 | 144篇 |
1975年 | 134篇 |
1974年 | 176篇 |
1973年 | 146篇 |
排序方式: 共有10000条查询结果,搜索用时 23 毫秒
61.
62.
G. N. Reiner L. Delgado-Marín N. Olguín S. Sánchez-Redondo M. Sánchez-Borzone E. Rodríguez-Farré C. Suñol D. A. García 《Cell biochemistry and biophysics》2013,67(2):515-525
Phenol compounds, such as propofol and thymol, have been shown to act on the GABAA receptor through interaction with specific sites of this receptor. In addition, considering the high lipophilicity of phenols, it is possible that their pharmacological activity may also be the result of the interaction of phenol molecules with the surrounding lipid molecules, modulating the supramolecular organization of the receptor environment. Thus, in the present study, we study the pharmacological activity of some propofol- and thymol-related phenols on the native GABAA receptor using primary cultures of cortical neurons and investigate the effects of these compounds on the micro viscosity of artificial membranes by means of fluorescence anisotropy. The phenol compounds analyzed in this article are carvacrol, chlorothymol, and eugenol. All compounds were able to enhance the binding of [3H]flunitrazepam with EC50 values in the micromolar range and to increase the GABA-evoked Cl? influx in a concentration-dependent manner, both effects being inhibited by the competitive GABAA antagonist bicuculline. These results strongly suggest that the phenols studied are positive allosteric modulators of this receptor. Chlorothymol showed a bell-type effect, reducing its positive effect at concentrations >100 μM. The concentrations necessary to induce positive allosteric modulation of GABAA receptor were not cytotoxic. Although all compounds were able to decrease the micro viscosity of artificial membranes, chlorothymol displayed a larger effect which could explain its effects on [3H]flunitrazepam binding and on cell viability at high concentrations. Finally, it is suggested that these compounds may exert depressant activity on the central nervous system and potentiate the effects of general anesthetics. 相似文献
63.
64.
Strain LSJC7, with dual resistance to arsenic and tetracycline, was isolated from an antimony tailing in China. Its 16S rRNA gene sequence has the highest similarity to that of Enterobacter cloacae subsp. dissolvens LMG 2683T (97.02%). Here we present the approximately 4.6-Mbp draft genome sequence of strain LSJC7. 相似文献
65.
M Bernard P Canioni P Cozzone J Berthou P Jollès 《International journal of peptide and protein research》1990,36(1):46-55
Carbon-13 NMR spectroscopy has been used to further document the interaction, at low and high temperatures, of N-acetylglucosamine and its short polymers with hen egg-white lysozyme. The results have been compared with the corresponding X-ray crystallographic data. Two domains, the active site and the hydrophobic box, have been found by NMR to undergo conformational rearrangement while X-ray crystallography only detected changes located in the active site. The extent of the modifications induced by inhibitor binding was proportional to the inhibitor size. The two techniques concurred to show that even in the presence of monosaccharide (N-acetylglucosamine), more than one subsite of the enzyme was occupied at high temperature, the binding at the C-site being the best defined. The thermal transition of lysozyme still occurred in solution when inhibitors were bound. However, in the solid state, crystallographic data showed that the transition was hindered. 相似文献
66.
Cells respond to chemokine stimulation by losing their round shape in a process called polarization, and by altering the subcellular localization of many proteins. Classic imaging techniques have been used to study these phenomena. However, they required the manual acquisition of many cells followed by time consuming quantification of the morphology and the co-localization of the staining of tens of cells. Here, a rapid and powerful method is described to study these phenomena on samples consisting of several thousands of cells using an imaging flow cytometry technology that combines the advantages of a microscope with those of a cytometer. Using T lymphocytes stimulated with CCL19 and staining for MHC Class I molecules and filamentous actin, a gating strategy is presented to measure simultaneously the degree of shape alterations and the extent of co-localization of markers that are affected by CCL19 signaling. Moreover, this gating strategy allowed us to observe the segregation of filamentous actin (at the front) and phosphorylated Ezrin-Radixin-Moesin (phospho-ERM) proteins (at the rear) in polarized T cells after CXCL12 stimulation. This technique was also useful to observe the blocking effect on polarization of two different elements: inhibition of actin polymerization by a pharmacological inhibitor and expression of mutants of the Par6/atypical PKC signaling pathway. Thus, evidence is shown that this technique is useful to analyze both morphological alterations and protein redistributions. 相似文献
67.
The environmental conditions to which juvenile barnacle geese (Branta leucopsis) were exposed during growth were found to affect their body size at fledging as well as their final adult body size. Small juveniles showed compensatory growth from the time of fledging up to one year of age, but this did not fully compensate the differences in body size that were established before fledging. The variation in protein content in plants eaten during growth could probably explain the observed body size differences, sometimes of more than 10%, between different categories of adult geese. Our results imply that one cannot infer selection on morphological characters from differences between samples of adult birds from different localities or from different cohorts within a population, without first showing that environmental conditions during growth do not affect the development of the characters under study. 相似文献
68.
Mathieu Lefèvre Daniel J. Felmlee Marie Parnot Thomas F. Baumert Catherine Schuster 《PloS one》2014,9(4)
Hepatitis C virus (HCV) is a major cause of liver disease worldwide and HCV infection represents a major health problem. HCV associates with host lipoproteins forming host/viral hybrid complexes termed lipoviral particles. Apolipoprotein E (apoE) is a lipoprotein component that interacts with heparan sulfate proteoglycans (HSPG) to mediate hepatic lipoprotein uptake, and may likewise mediate HCV entry. We sought to define the functional regions of apoE with an aim to identify critical apoE binding partners involved in HCV infection. Using adenoviral vectors and siRNA to modulate apoE expression we show a direct correlation of apoE expression and HCV infectivity, whereas no correlation exists with viral protein expression. Mutating the HSPG binding domain (HSPG-BD) of apoE revealed key residues that are critical for mediating HCV infection. Furthermore, a novel synthetic peptide that mimics apoE’s HSPG-BD directly and competitively inhibits HCV infection. Genetic knockdown of the HSPG proteins syndecan (SDC) 1 and 4 revealed that SDC4 principally mediates HCV entry. Our data demonstrate that HCV uses apoE-SDC4 interactions to enter hepatoma cells and establish infection. Targeting apoE-SDC interactions could be an alternative strategy for blocking HCV entry, a critical step in maintaining chronic HCV infection. 相似文献
69.
Four main molecular forms of acetylcholinesterase (AChE) can be solubilized from newborn rat superior cervical ganglia (SCG), homogenized in the presence of a high-ionic-strength, detergent-containing medium. These forms, respectively referred to as 16, 10, 6.5, and 4 S, are characterized by their sedimentation coefficients. Their relative proportions in SCG are notably different in vivo during postnatal maturation, and in culture. The 16-S AChE appears to be mainly neuronal in origin, is maintained in culture independently of original presynaptic in vivo elements, and its cellular pool is not depleted in the presence of tetrodotoxin (TTX). 相似文献
70.
Administration of choline chloride i.p. to rats causes a dose-dependent increase in the brain concentration of the neurotransmitter, acetylcholine (ACh). This increase is maximal (22% after a 60-mg/kg dose) 40 minutes after injection. These observations suggest that precursor availability may influence brain ACh synthesis, just as brain tryptophan and tyrosine levels have previously been shown to control the synthesis of brain serotonin and catecholamines. 相似文献