全文获取类型
收费全文 | 8112篇 |
免费 | 657篇 |
国内免费 | 592篇 |
出版年
2024年 | 4篇 |
2023年 | 86篇 |
2022年 | 122篇 |
2021年 | 417篇 |
2020年 | 306篇 |
2019年 | 346篇 |
2018年 | 370篇 |
2017年 | 251篇 |
2016年 | 356篇 |
2015年 | 504篇 |
2014年 | 571篇 |
2013年 | 601篇 |
2012年 | 765篇 |
2011年 | 640篇 |
2010年 | 386篇 |
2009年 | 373篇 |
2008年 | 410篇 |
2007年 | 384篇 |
2006年 | 349篇 |
2005年 | 277篇 |
2004年 | 238篇 |
2003年 | 204篇 |
2002年 | 176篇 |
2001年 | 144篇 |
2000年 | 115篇 |
1999年 | 133篇 |
1998年 | 79篇 |
1997年 | 91篇 |
1996年 | 79篇 |
1995年 | 74篇 |
1994年 | 85篇 |
1993年 | 60篇 |
1992年 | 73篇 |
1991年 | 69篇 |
1990年 | 60篇 |
1989年 | 33篇 |
1988年 | 38篇 |
1987年 | 25篇 |
1986年 | 19篇 |
1985年 | 23篇 |
1984年 | 9篇 |
1983年 | 11篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
排序方式: 共有9361条查询结果,搜索用时 31 毫秒
991.
Alzheimer's disease is characterized by progressive loss of neurons accompanied by the formation of intraneural neurofibrillary tangles and extracellular amyloid plaques. Human neuronal growth inhibitory factor, classified as metallothionein-3 (MT-3), was found to be related to the neurotrophic activity promoting cortical neuron survival and dendrite outgrowth in the cell culture studies. We have determined the solution structure of the alpha-domain of human MT-3 (residues 32-68) by multinuclear and multidimensional NMR spectroscopy in combination with the molecular dynamic simulated annealing approach. The human MT-3 shows two metal-thiolate clusters, one in the N-terminus (beta-domain) and one in the C-terminus (alpha-domain). The overall fold of the alpha-domain is similar to that of mouse MT-3. However, human MT-3 has a longer loop in the acidic hexapeptide insertion than that of mouse MT-3. Surprisingly, the backbone dynamics of the protein revealed that the beta-domain exhibits similar internal motion to the alpha-domain, although the N-terminal residues are more flexible. Our results may provide useful information for understanding the structure-function relationship of human MT-3. 相似文献
992.
Genomewide screen reveals a wide regulatory network for di/tripeptide utilization in Saccharomyces cerevisiae 下载免费PDF全文
Small peptides of two to six residues serve as important sources of amino acids and nitrogen required for growth by a variety of organisms. In the yeast Saccharomyces cerevisiae, the membrane transport protein Ptr2p, encoded by PTR2, mediates the uptake of di/tripeptides. To identify genes involved in regulation of dipeptide utilization, we performed a systematic, functional examination of this process in a haploid, nonessential, single-gene deletion mutant library. We have identified 103 candidate genes: 57 genes whose deletion decreased dipeptide utilization and 46 genes whose deletion enhanced dipeptide utilization. On the basis of Ptr2p-GFP expression studies, together with PTR2 expression analysis and dipeptide uptake assays, 42 genes were ascribed to the regulation of PTR2 expression, 37 genes were involved in Ptr2p localization, and 24 genes did not apparently affect Ptr2p-GFP expression or localization. The 103 genes regulating dipeptide utilization were distributed among most of the Gene Ontology functional categories, indicating a very wide regulatory network involved in transport and utilization of dipeptides in yeast. It is anticipated that further characterization of how these genes affect peptide utilization should add new insights into the global mechanisms of regulation of transport systems in general and peptide utilization in particular. 相似文献
993.
Liquid chromatography coupled with mass spectrometry and tandem mass spectrometry has been applied to investigate the in vivo metabolism of ginsenoside Rb(1) in rat. Both positive electrospray ionization mass spectrometry and negative electrospray ionization mass spectrometry were used to identify the Rb(1) and its metabolites in rat plasma, urine, and feces samples. Oxygenation and deglycosylation were found to be the major metabolic pathways of Rb(1) in rat. A total of nine metabolites were detected in urine and feces samples collected after intravenous and oral administration. Deglycosylated metabolism of Rb(1) generated other ginsenosides as the major metabolites, such as Rd, Rg(3) or F(2), Rh(2), or C-K. This result indicates that the ginsenoside Rb(1) has many pharmacological activities and could be used as a prodrug. 相似文献
994.
Variation between freshwater and terrestrial fungal communities on decaying bamboo culms 总被引:1,自引:0,他引:1
Fungal communities on decaying culms of a bamboo host (Phyllostachys bambusoides) from freshwater and adjacent terrestrial habitats were identified. Collections were made at Xiao Bai Long Mountain, Yiliang,
Yunnan, China in the winter and summer. In each collection, 100 similar-sized bamboo culms were collected, comprising 50 submerged
samples from a stream and 50 terrestrial samples from adjacent riparian vegetation. A total of 82 fungal taxa were recorded
from the samples, including 30 ascomycetes and 52 anamorphic fungi. The frequency of occurrence of these fungi were recorded
and the Shannon–Weiner indices (H′) were applied to evaluate fungal diversity. The results showed that variation of the fungal diversity between the summer
and winter collections was insignificant (0.2<p<0.5). Fungal diversity on submerged bamboo however, was significantly higher than that on terrestrial bamboo (p<0.001). Further findings were that: (1) some commonly recorded freshwater and terrestrial taxa were found in both habitats,
but overall there were only 15 overlapping species between the two habitats; (2) the dominant species in each habitat were
considerably different, and (3) only a few fungi were dominant, while most species were rare, being recorded only once or
twice. Factors responsible for the distribution patterns and variations in composition of the fungal communities are discussed. 相似文献
995.
Prediction of protease types in a hybridization space 总被引:2,自引:0,他引:2
Regulating most physiological processes by controlling the activation, synthesis, and turnover of proteins, proteases play pivotal regulatory roles in conception, birth, digestion, growth, maturation, ageing, and death of all organisms. Different types of proteases have different functions and biological processes. Therefore, it is important for both basic research and drug discovery to consider the following two problems. (1) Given the sequence of a protein, can we identify whether it is a protease or non-protease? (2) If it is, what protease type does it belong to? Although the two problems can be solved by various experimental means, it is both time-consuming and costly to do so. The avalanche of protein sequences generated in the post-genetic era has challenged us to develop an automated method for making a fast and reliable identification. By hybridizing the functional domain composition and pseudo-amino acid composition, we have introduced a new method called "FunD-PseAA predictor" that is operated in a hybridization space. To avoid redundancy and bias, demonstrations were performed on a dataset where none of the proteins has >or=25% sequence identity to any other. The overall success rate thus obtained by the jackknife cross-validation test in identifying protease and non-protease was 92.95%, and that in identifying the protease type was 94.75% among the following six types: (1) aspartic, (2) cysteine, (3) glutamic, (4) metallo, (5) serine, and (6) threonine. Demonstration was also made on an independent dataset, and the corresponding overall success rates were 98.36% and 97.11%, respectively, suggesting the FunD-PseAA predictor is very powerful and may become a useful tool in bioinformatics and proteomics. 相似文献
996.
Tian J Cai T Yuan Z Wang H Liu L Haas M Maksimova E Huang XY Xie ZJ 《Molecular biology of the cell》2006,17(1):317-326
We have shown that ouabain activates Src, resulting in subsequent tyrosine phosphorylation of multiple effectors. Here, we tested if the Na+/K+-ATPase and Src can form a functional signaling complex. In LLC-PK1 cells the Na+/K+-ATPase and Src colocalized in the plasma membrane. Fluorescence resonance energy transfer analysis indicated that both proteins were in close proximity, suggesting a direct interaction. GST pulldown assay showed a direct, ouabain-regulated, and multifocal interaction between the 1 subunit of Na+/K+-ATPase and Src. Although the interaction between the Src kinase domain and the third cytosolic domain (CD3) of 1 is regulated by ouabain, the Src SH3SH2 domain binds to the second cytosolic domain constitutively. Functionally, binding of Src to either the Na+/K+-ATPase or GST-CD3 inhibited Src activity. Addition of ouabain, but not vanadate, to the purified Na+/K+-ATPase/Src complex freed the kinase domain and restored the Src activity. Consistently, exposure of intact cells to ouabain apparently increased the distance between the Na+/K+-ATPase and Src. Concomitantly, it also stimulated tyrosine phosphorylation of the proteins that are associated with the Na+/K+-ATPase. These new findings illustrate a novel molecular mechanism of signal transduction involving the interaction of a P-type ATPase and a nonreceptor tyrosine kinase. 相似文献
997.
Development of the multilayered cerebral cortex involves extensive regulated migration of neurons arising from the deeper germinative layers of the mammalian brain. The anatomy and formation of the cortical layers has been well characterized; however, the underlying molecular mechanisms that control the migration and the final positioning of neurons within the cortex remain poorly understood. Here, we report evidence for a key role of Ena/VASP proteins, a protein family implicated in the spatial control of actin assembly and previously shown to negatively regulate fibroblast cell speeds, in cortical development. Ena/VASP proteins are highly expressed in the developing cortical plate in cells bordering Reelin-expressing Cajal-Retzius cells and in the intermediate zone through which newly born cells migrate. Inhibition of Ena/VASP function through retroviral injections in utero led to aberrant placement of early-born pyramidal neurons in the superficial layers of both the embryonic and the postnatal cortex in a cell-autonomous fashion. The abnormally placed pyramidal neurons exhibited grossly normal morphology and polarity. Our results are consistent with a model in which Ena/VASP proteins function in vivo to control the position of neurons in the mouse neocortex. 相似文献
998.
999.
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of a family of membrane proteins, called GABA transporters (GAT1-4). It is well established that GABA system is involved in the modulation of memory. Our previous study showed that homozygous GAT1(-/-) mice exhibited impaired hippocampus-dependent learning and memory. To evaluate the impact of endogenous reduced GABA reuptake on mice cognitive behaviors, the ability of learning and memory of heterozygous GAT1(+/-) mice was detected by the passive avoidance paradigm and Morris water maze. The hole board paradigm was also used to measure changes in anxiety-related behavior or exploratory behavior in such mice. As one form of synaptic plasticity, long-term potentiation was recorded in the mouse hippocampal CA1 area. We found that GAT1(+/-) mice displayed increased learning and memory, decreased anxiety-like behaviors, and highest synaptic plasticity compared with wild-type and homozygous GAT1(-/-) mice. Our results suggest that a moderate reduction in GAT1 activity causes the enhancement of learning and memory in mice. 相似文献
1000.
Li J Sun L Xu C Yu F Zhou H Zhao Y Zhang J Cai J Mao C Tang L Xu Y He J 《生物化学与生物物理学报(英文版)》2012,44(4):300-306
The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity. 相似文献