全文获取类型
收费全文 | 4009篇 |
免费 | 289篇 |
国内免费 | 1篇 |
专业分类
4299篇 |
出版年
2023年 | 21篇 |
2022年 | 55篇 |
2021年 | 110篇 |
2020年 | 61篇 |
2019年 | 60篇 |
2018年 | 91篇 |
2017年 | 69篇 |
2016年 | 122篇 |
2015年 | 195篇 |
2014年 | 187篇 |
2013年 | 273篇 |
2012年 | 316篇 |
2011年 | 350篇 |
2010年 | 198篇 |
2009年 | 175篇 |
2008年 | 223篇 |
2007年 | 271篇 |
2006年 | 263篇 |
2005年 | 218篇 |
2004年 | 244篇 |
2003年 | 209篇 |
2002年 | 204篇 |
2001年 | 30篇 |
2000年 | 18篇 |
1999年 | 28篇 |
1998年 | 42篇 |
1997年 | 25篇 |
1996年 | 27篇 |
1995年 | 25篇 |
1994年 | 13篇 |
1993年 | 19篇 |
1992年 | 19篇 |
1991年 | 12篇 |
1990年 | 14篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 10篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 12篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1968年 | 3篇 |
1966年 | 3篇 |
排序方式: 共有4299条查询结果,搜索用时 15 毫秒
31.
32.
33.
Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes 总被引:7,自引:0,他引:7
Madakamutil LT Maricic I Sercarz E Kumar V 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(6):2985-2992
Clinical autoimmunity requires both activation of self-reactive T cells as well as a failure of peripheral tolerance mechanisms. We previously identified one such mechanism that involves regulatory T cells recognizing TCR V beta 8.2 chain-derived peptides in the context of MHC. How this regulation affects the fate of target V beta 8.2(+) T lymphocytes in vivo that mediate experimental autoimmune encephalomyelitis has remained unknown. The present study using immunoscope and CFSE-labeling analysis demonstrates that the expansion of regulatory CD4 and CD8 T cells in vivo results in apoptotic depletion of the dominant, myelin basic protein-reactive V beta 8.2(+) T cells, but not subdominant V beta 13(+) T cells. The elimination of only activated T cells by this negative feedback mechanism preserves the remainder of the naive V beta 8.2(+) T cell repertoire and at the same time results in protection from disease. These studies are the first in clearly elucidating the fate of myelin basic protein-specific encephalitogenic T cells in vivo following regulation. 相似文献
34.
35.
36.
Second Messengers Mediate Increases in Cytosolic Calcium in
Tobacco Protoplasts 总被引:12,自引:2,他引:12 下载免费PDF全文
Igor D. Volotovski Sergei G. Sokolovsky Olga V. Molchan Marc R. Knight 《Plant physiology》1998,117(3):1023-1030
Addition of membrane-permeable cyclic GMP (cGMP) and cyclic AMP (cAMP) were shown to cause elevation of cytosolic Ca2+ concentration ([Ca2+]cyt) in tobacco (Nicotiana plumbaginofolia) protoplasts. Under the same conditions these cyclic nucleotides were shown to provoke a physiological swelling response in the protoplasts. Nonmembrane-permeable cAMP and cGMP were unable to trigger a detectable [Ca2+]cyt response. Cyclic-nucleotide-mediated elevations in [Ca2+]cyt involved both internal and external Ca2+ stores. Both cAMP- and cGMP-mediated [Ca2+]cyt elevations could be inhibited by the Ca2+-channel blocker verapamil. Addition of inhibitors of phosphodiesterases (isobutylmethylxanthine and zaprinast) and the adenylate cyclase agonist forskolin to the protoplasts (predicted to elevate in vivo cyclic-nucleotide concentrations) caused elevations in [Ca2+]cyt. Addition of the adenylate cyclase inhibitor 2′,5′-dideoxyadenosine before forskolin significantly inhibited the forskolin-induced [Ca2+]cyt elevation. Taken together, these data suggest that a potential communication point for cross-talk between signal transduction pathways using cyclic nucleotides in plants is at the level of Ca2+ signaling. 相似文献
37.
This article describes DP-Bind, a web server for predicting DNA-binding sites in a DNA-binding protein from its amino acid sequence. The web server implements three machine learning methods: support vector machine, kernel logistic regression and penalized logistic regression. Prediction can be performed using either the input sequence alone or an automatically generated profile of evolutionary conservation of the input sequence in the form of PSI-BLAST position-specific scoring matrix (PSSM). PSSM-based kernel logistic regression achieves the accuracy of 77.2%, sensitivity of 76.4% and specificity of 76.6%. The outputs of all three individual methods are combined into a consensus prediction to help identify positions predicted with high level of confidence. AVAILABILITY: Freely available at http://lcg.rit.albany.edu/dp-bind. SUPPLEMENTARY INFORMATION: http://lcg.rit.albany.edu/dp-bind/dpbind_supplement.html. 相似文献
38.
Christian M. Paumi Matthew Chuk Jamie Snider Igor Stagljar Susan Michaelis 《Microbiology and molecular biology reviews》2009,73(4):577-593
Summary: Members of the ATP-binding cassette (ABC) transporter superfamily exist in bacteria, fungi, plants, and animals and play key roles in the efflux of xenobiotic compounds, physiological substrates, and toxic intracellular metabolites. Based on sequence relatedness, mammalian ABC proteins have been divided into seven subfamilies, ABC subfamily A (ABCA) to ABCG. This review focuses on recent advances in our understanding of ABC transporters in the model organism Saccharomyces cerevisiae. We propose a revised unified nomenclature for the six yeast ABC subfamilies to reflect the current mammalian designations ABCA to ABCG. In addition, we specifically review the well-studied yeast ABCC subfamily (formerly designated the MRP/CFTR subfamily), which includes six members (Ycf1p, Bpt1p, Ybt1p/Bat1p, Nft1p, Vmr1p, and Yor1p). We focus on Ycf1p, the best-characterized yeast ABCC transporter. Ycf1p is located in the vacuolar membrane in yeast and functions in a manner analogous to that of the human multidrug resistance-related protein (MRP1, also called ABCC1), mediating the transport of glutathione-conjugated toxic compounds. We review what is known about Ycf1p substrates, trafficking, processing, posttranslational modifications, regulation, and interactors. Finally, we discuss a powerful new yeast two-hybrid technology called integrated membrane yeast two-hybrid (iMYTH) technology, which was designed to identify interactors of membrane proteins. iMYTH technology has successfully identified novel interactors of Ycf1p and promises to be an invaluable tool in future efforts to comprehensively define the yeast ABC interactome. 相似文献
39.
A previously introduced kinetic-rate constant (k/k(0)) method, where k and k(0) are the folding (unfolding) rate constants in the mutant and the wild-type forms, respectively, of a protein, has been applied to obtain qualitative information about structure in the transition state ensemble (TSE) of bovine pancreatic ribonuclease A (RNase A), which contains four native disulfide bonds. The method compares the folding (unfolding) kinetics of RNase A, with and without a covalent crosslink and tests whether the crosslinked residues are associated in the folding (unfolding) transition state (TS) of the noncrosslinked version. To confirm that the fifth disulfide bond has not introduced a significant structural perturbation, we solved the crystal structure of the V43C-R85C mutant to 1.6 A resolution. Our findings suggest that residues Val43 and Arg85 are not associated, and that residues Ala4 and Val118 may form nonnative contacts, in the folding (unfolding) TSE of RNase A. 相似文献
40.
Yan BS Pichugin AV Jobe O Helming L Eruslanov EB Gutiérrez-Pabello JA Rojas M Shebzukhov YV Kobzik L Kramnik I 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(10):6919-6932
Using a mouse model for genetic analysis of host resistance to virulent Mycobacterium tuberculosis, we have identified a genetic locus sst1 on mouse chromosome 1, which controls progression of pulmonary tuberculosis. In vitro, this locus had an effect on macrophage-mediated control of two intracellular bacterial pathogens, M. tuberculosis and Listeria monocytogenes. In this report, we investigated a specific function of the sst1 locus in antituberculosis immunity in vivo, especially its role in control of pulmonary tuberculosis. We found that the sst1 locus affected neither activation of Th1 cytokine-producing T lymphocytes, nor their migration to the lungs, but rather controlled an inducible NO synthase-independent mechanism of innate immunity. Although the sst1(S) macrophages responded to stimulation with IFN-gamma in vitro, their responsiveness to activation by T cells was impaired. Boosting T cell-mediated immunity by live attenuated vaccine Mycobacterium bovis bacillus Calmette-Guérin or the adoptive transfer of mycobacteria-activated CD4(+) T lymphocytes had positive systemic effect, but failed to improve control of tuberculosis infection specifically in the lungs of the sst1(S) animals. Thus, in the mouse model of tuberculosis, a common genetic mechanism of innate immunity mediated control of tuberculosis progression in the lungs and the efficiency of antituberculosis vaccine. Our data suggest that in immunocompetent humans the development of pulmonary tuberculosis and the failure of the existing vaccine to protect against it, in some cases, may be explained by a similar defect in a conserved inducible NO synthase-independent mechanism of innate immunity, either inherited or acquired. 相似文献