全文获取类型
收费全文 | 46101篇 |
免费 | 96篇 |
国内免费 | 118篇 |
专业分类
系统科学 | 358篇 |
丛书文集 | 1082篇 |
教育与普及 | 118篇 |
理论与方法论 | 246篇 |
现状及发展 | 20284篇 |
研究方法 | 1719篇 |
综合类 | 21805篇 |
自然研究 | 703篇 |
出版年
2013年 | 286篇 |
2012年 | 577篇 |
2011年 | 1310篇 |
2010年 | 249篇 |
2008年 | 748篇 |
2007年 | 786篇 |
2006年 | 842篇 |
2005年 | 837篇 |
2004年 | 779篇 |
2003年 | 832篇 |
2002年 | 758篇 |
2001年 | 1358篇 |
2000年 | 1240篇 |
1999年 | 804篇 |
1992年 | 799篇 |
1991年 | 677篇 |
1990年 | 718篇 |
1989年 | 669篇 |
1988年 | 693篇 |
1987年 | 713篇 |
1986年 | 690篇 |
1985年 | 855篇 |
1984年 | 699篇 |
1983年 | 589篇 |
1982年 | 495篇 |
1981年 | 511篇 |
1980年 | 665篇 |
1979年 | 1422篇 |
1978年 | 1214篇 |
1977年 | 1207篇 |
1976年 | 876篇 |
1975年 | 996篇 |
1974年 | 1375篇 |
1973年 | 1204篇 |
1972年 | 1221篇 |
1971年 | 1482篇 |
1970年 | 1942篇 |
1969年 | 1503篇 |
1968年 | 1368篇 |
1967年 | 1450篇 |
1966年 | 1257篇 |
1965年 | 907篇 |
1964年 | 243篇 |
1959年 | 571篇 |
1958年 | 850篇 |
1957年 | 668篇 |
1956年 | 572篇 |
1955年 | 503篇 |
1954年 | 561篇 |
1948年 | 334篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Antigen presentation. The second class story 总被引:4,自引:0,他引:4
R N Germain 《Nature》1991,353(6345):605-607
992.
993.
本文研究了AVCO碳化硅(SCS-6)单丝纤维的热性能、热暴露后的表面形态和氧化现象以及断口形貌,并对SiC的主动氧化和被动氧化进行了分析,得出了纤维的力学性能与其氧化现象的必然联系。 相似文献
994.
Mutational analysis of a protein-folding pathway 总被引:6,自引:0,他引:6
The effects of amino-acid replacements on the disulphide-coupled folding pathway of bovine pancreatic trypsin inhibitor have been examined. Replacements at three sites destabilize the native protein relative to the unfolded state, but have different effects on the relative stabilities of the disulphide-bonded folding intermediates, thus allowing the roles of the altered residues during folding to be distinguished. 相似文献
995.
Inhibition of endocytic vesicle fusion in vitro by the cell-cycle control protein kinase cdc2 总被引:3,自引:0,他引:3
Membrane transport between the endoplasmic reticulum and the plasma membrane, which involves the budding and fusion of carrier vesicles, is inhibited during mitosis in animal cells. At the same time, the Golgi complex and the nuclear envelope, as well as the endoplasmic reticulum in some cell types, become fragmented. Fragmentation of the Golgi is believed to facilitate its equal partitioning between daughter cells. In fact, it has been postulated that both the inhibition of membrane traffic and Golgi fragmentation during mitosis are due to an inhibition of vesicle fusion, while vesicle budding continues. Although less is known about the endocytic pathway, internalization and receptor recycling are also arrested during mitosis. We have now used a cell-free assay to show that the fusion of endocytic vesicles from baby hamster kidney cells is reduced in Xenopus mitotic cytosol when compared with interphase cytosol. We reconstituted this inhibition in interphase cytosol by adding a preparation enriched in the starfish homologue of the cdc2 protein kinase. Inhibition was greater than or equal to 90% when the added cdc2 activity was in the range estimated for that in mitotic Xenopus eggs, which indicates that during mitosis the cdc2 kinase mediates an inhibition of endocytic vesicle fusion, and possibly other fusion events in membrane traffic. 相似文献
996.
Phenotypic differences between alpha beta versus beta T-cell receptor transgenic mice undergoing negative selection 总被引:8,自引:0,他引:8
T-cell differentiation in the thymus is thought to involve a progression from the CD4-CD8- phenotype through CD4+CD8+ intermediates to mature CD4+ or CD8+ cells. There is evidence that during this process T cells bearing receptors potentially reactive to 'self' are deleted by a process termed 'negative selection' One example of this process occurs in mice carrying polymorphic Mls antigens, against which a detectable proportion of T cells are autoreactive. These mice show clonal deletion of thymic and peripheral T-cell subsets that express the autoreactive V beta 3 segment of the T-cell antigen receptor, but at most a two-fold depletion of thymic cells at the CD4+CD8+ stage. By contrast, transgenic mice bearing both alpha and beta chain genes encoding autoreactive receptors recognizing other ligands, show severe depletion of CD4+CD8+ thymocytes as well, suggesting that negative selection occurs much earlier. We report here the Mls 2a/3a mediated elimination of T cells expressing a transgene encoded V beta 3-segment, in T-cell receptor alpha/beta and beta-transgenic mice. Severe depletion of CD4+CD8+ thymocytes is seen only in the alpha/beta chain transgenic mice, whereas both strains delete mature V beta 3 bearing CD4+ and CD8+ T cells efficiently. We conclude that severe CD4+CD8+ thymocyte deletion in alpha/beta transgenic mice results from the premature expression of both receptor chains, and does not reflect a difference in the timing or mechanism of negative selection for Mls antigens as against the allo- and MHC class 1-restricted antigens used in the other studies. 相似文献
997.
D B Pritchett H Sontheimer B D Shivers S Ymer H Kettenmann P R Schofield P H Seeburg 《Nature》1989,338(6216):582-585
Neurotransmission effected by GABA (gamma-aminobutyric acid) is predominantly mediated by a gated chloride channel intrinsic to the GABAA receptor. This heterooligomeric receptor exists in most inhibitory synapses in the vertebrate central nervous system (CNS) and can be regulated by clinically important compounds such as benzodiazepines and barbiturates. The primary structures of GABAA receptor alpha- and beta-subunits have been deduced from cloned complementary DNAs. Co-expression of these subunits in heterologous systems generates receptors which display much of the pharmacology of their neural counterparts, including potentiation by barbiturates. Conspicuously, however, they lack binding sites for, and consistent electrophysiological responses to, benzodiazepines. We now report the isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed gamma 2, which shares approximately 40% sequence identity with alpha- and beta-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS. Importantly, coexpression of the gamma 2 subunit with alpha 1 and beta 1 subunits produces GABAA receptors displaying high-affinity binding for central benzodiazepine receptor ligands. 相似文献
998.
Arginine vasopressin enhances pHi regulation in the presence of HCO3- by stimulating three acid-base transport systems 总被引:14,自引:0,他引:14
Growth factors raise intracellular pH (pHi) by stimulating Na+/H+ exchange in the absence of HCO3-. In mutant cells that lack the Na+/H+ exchange activity, this alkalinization does not occur, and the cells do not proliferate without artificial elevation of pHi. It has therefore been widely suggested that an early pHi increase is a necessary signal for mitogenesis. In the presence of HCO3- however, growth factors fail to raise pHi in A431 cells, renal mesangial cells and 3T3 fibroblasts. In mesangial cells, arginine vasopressin (AVP) raises pHi in the absence of HCO3-, but lowers it when HCO3- is present; growth is stimulated under both conditions. We report here that, in the presence of HCO3-, AVP stimulates two potent HCO3- transporters, as well as the Na+/H+ exchanger. These are the Na+-dependent and Na+-independent Cl-/HCO3- exchangers. Our results indicate that AVP causes acidification in the presence of HCO3- because, at the resting pHi, it stimulates Na+-independent Cl-/HCO3- exchange (which lowers pHi) more than it stimulates the sum of Na+/H+ exchange and Na+-dependent Cl-/HCO3- exchange (both of which raise pHi). The stimulation of three acid-base transporters by the growth factor AVP greatly enhances the ability of the cell to regulate pHi. 相似文献
999.
Positive selection of CD4+ T cells mediated by MHC class II-bearing stromal cell in the thymic cortex 总被引:12,自引:0,他引:12
T lymphocytes differentiate in the thymus, where functionally immature, CD4+CD8+ (double positive) thymocytes develop into functionally mature CD4+ helper cells and CD8+ cytotoxic (single positive) T cells. The thymus is the site where self-reactive T cells are negatively selected (clonally deleted) and where T cells with the capacity to recognize foreign antigens in association with self-proteins encoded by the major histocompatibility complex (MHC) are positively selected. The net result of these developmental pathways is a T-cell repertoire that is both self-tolerant and self-restricted. One unresolved issue is the identity of the thymic stromal cells that mediate the negative and positive selection of the T-cell repertoire. Previous work has pointed to a bone-marrow-derived macrophage or dendritic cell as the inducer of tolerance, whereas a radiation-resistant, deoxyguanosine-resistant thymic cell seems to mediate the positive selection of self-MHC restricted T cells. Thymic stromal cells in the cortex interact with the T-cell antigen receptor on thymocytes. Using several strains of transgenic mice that express the class II MHC molecule I-E in specific regions of the thymus, we show directly that the positive selection of T cells is mediated by an I-E-bearing cell in the thymic cortex. 相似文献
1000.
Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells 总被引:47,自引:0,他引:47
Tolerance to self-antigens has been shown to develop during ontogeny as a result of the clonal deletion of self-reactive T cells. Tolerance, or better 'nonresponsiveness', to specific antigens can also be induced in adult animals but the mechanism(s) involved are not well understood. Most murine T-helper cells that express the V beta 6 T-cell receptor gene segment are specific for Mls-1a antigens. We have therefore been able to use an anti-V beta 6 monoclonal antibody to follow the fate of Mls-1a specific T cells in adult Mls-1b mice made specifically unresponsive to Mls-1a. We show that the induced unresponsiveness is not due to clonal deletion, but rather to clonal anergy. The anergic V beta 6 T-helper cells express IL-2 receptors and undergo limited blastogenesis in vitro upon stimulation, but do not produce IL-2, in marked contrast to V beta 6 cells from naive mice. Our data appear to represent an in vivo correlate for the induction of anergy that has been observed in T-cell lines in vitro. 相似文献