全文获取类型
收费全文 | 35609篇 |
免费 | 112篇 |
国内免费 | 102篇 |
专业分类
系统科学 | 345篇 |
丛书文集 | 858篇 |
教育与普及 | 78篇 |
理论与方法论 | 109篇 |
现状及发展 | 15886篇 |
研究方法 | 1304篇 |
综合类 | 16747篇 |
自然研究 | 496篇 |
出版年
2012年 | 432篇 |
2011年 | 966篇 |
2010年 | 193篇 |
2009年 | 182篇 |
2008年 | 551篇 |
2007年 | 634篇 |
2006年 | 606篇 |
2005年 | 620篇 |
2004年 | 548篇 |
2003年 | 601篇 |
2002年 | 504篇 |
2001年 | 1103篇 |
2000年 | 1121篇 |
1999年 | 655篇 |
1992年 | 649篇 |
1991年 | 547篇 |
1990年 | 585篇 |
1989年 | 519篇 |
1988年 | 555篇 |
1987年 | 568篇 |
1986年 | 552篇 |
1985年 | 715篇 |
1984年 | 528篇 |
1983年 | 451篇 |
1982年 | 397篇 |
1981年 | 435篇 |
1980年 | 541篇 |
1979年 | 1135篇 |
1978年 | 929篇 |
1977年 | 924篇 |
1976年 | 726篇 |
1975年 | 813篇 |
1974年 | 1111篇 |
1973年 | 941篇 |
1972年 | 907篇 |
1971年 | 1093篇 |
1970年 | 1453篇 |
1969年 | 1187篇 |
1968年 | 1022篇 |
1967年 | 1075篇 |
1966年 | 951篇 |
1965年 | 694篇 |
1964年 | 182篇 |
1959年 | 419篇 |
1958年 | 652篇 |
1957年 | 461篇 |
1956年 | 408篇 |
1955年 | 369篇 |
1954年 | 400篇 |
1948年 | 253篇 |
排序方式: 共有10000条查询结果,搜索用时 125 毫秒
811.
Calcium/calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes 总被引:28,自引:0,他引:28
A variety of evidence indicates that calcium-dependent protein phosphorylation modulates the release of neurotransmitter from nerve terminals. For instance, the injection of rat calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-dependent PK II) into the preterminal digit of the squid giant synapse leads to an increase in the release of a so-far unidentified neurotransmitter induced by presynaptic depolarization. But until now, it has not been demonstrated that Ca2+/CaM-dependent PK II can also regulate neurotransmitter release in the vertebrate nervous system. Here we report that the introduction of Ca2+/CaM-dependent PK II, autoactivated by thiophosphorylation, into rat brain synaptosomes (isolated nerve terminals) increases the initial rate of induced release of two neurotransmitters, glutamate and noradrenaline. We also show that introduction of a selective peptidergic inhibitor of Ca2+/CaM-dependent PK II inhibits the initial rate of induced glutamate release. These results support the hypothesis that activation of Ca2+/CaM-dependent PK II in the nerve terminal removes a constraint on neurotransmitter release. 相似文献
812.
R D Salter R J Benjamin P K Wesley S E Buxton T P Garrett C Clayberger A M Krensky A M Norment D R Littman P Parham 《Nature》1990,345(6270):41-46
Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 alpha-chain binds to the alpha 3 domain of HLA-A2.1. Three clusters of alpha 3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation. 相似文献
813.
Nonlinear forecasting as a way of distinguishing chaos from measurement error in time series 总被引:49,自引:0,他引:49
An approach is presented for making short-term predictions about the trajectories of chaotic dynamical systems. The method is applied to data on measles, chickenpox, and marine phytoplankton populations, to show how apparent noise associated with deterministic chaos can be distinguished from sampling error and other sources of externally induced environmental noise. 相似文献
814.
Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3 总被引:16,自引:0,他引:16
L M Brzustowicz T Lehner L H Castilla G K Penchaszadeh K C Wilhelmsen R Daniels K E Davies M Leppert F Ziter D Wood 《Nature》1990,344(6266):540-541
SPINAL muscular atrophy (SMA) describes a group of heritable degenerative diseases that selectively affect the alpha-motor neuron. Childhood-onset SMAs rank second in frequency to cystic fibrosis among autosomal recessive disorders, and are the leading cause of heritable infant mortality. Predictions that genetic heterogeneity underlies the differences between types of SMA, together with the aggressive nature of the most-severe infantile form, make linkage analysis of SMA potentially complex. We have now analysed 13 clinically heterogeneous SMA families. We find that 'chronic' childhood-onset SMA (including intermediate SMA or SMA type II, and Kugelberg-Welander or SMA type III) is genetically homogeneous, mapping to chromosomal region 5q11.2-13.3. 相似文献
815.
816.
Protein engineering is being developed for mapping the energetics and pathway of protein folding. From kinetic studies on wild-type and mutant proteins, the sequence and energetics of formation of tertiary interactions of side chains can be mapped and the formation of secondary structure inferred. Here we cross-check and complement results from this approach by using a recently developed procedure that traps and characterizes secondary structure in intermediate states using 1H NMR. The refolding of barnase is shown to be a multiphasic process in which the secondary structure in alpha-helices and beta-sheets and some turns is formed more rapidly than is the overall folding. 相似文献
817.
Acute leukaemia in bcr/abl transgenic mice 总被引:38,自引:0,他引:38
N Heisterkamp G Jenster J ten Hoeve D Zovich P K Pattengale J Groffen 《Nature》1990,344(6263):251-253
818.
Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death 总被引:174,自引:0,他引:174
The t(14; 18) chromosomal translocation of human follicular B-cell lymphoma juxtaposes the bcl-2 gene with the immunoglobulin heavy chain locus. The bcl-2 immunoglobulin fusion gene is markedly deregulated resulting in inappropriately elevated levels of bcl-2 RNA and protein. Transgenic mice bearing a bcl-2 immunoglobulin minigene demonstrate a polyclonal expansion of resting yet responsive IgM-IgD B cells which display prolonged cell survival but no increase in cell cycling. Moreover, deregulated bcl-2 extends the survival of certain haematopoietic cell lines following growth-factor deprivation. By using immunolocalization studies we now demonstrate that Bcl-2 is an integral inner mitochondrial membrane protein of relative molecular mass 25,000 (25k). Overexpression of Bcl-2 blocks the apoptotic death of a pro-B-lymphocyte cell line. Thus, Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and interfering with programmed cell death independent of promoting cell division. 相似文献
819.
820.
Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C 总被引:43,自引:0,他引:43
Neurotransmitters are released at synapses by the Ca2(+)-regulated exocytosis of synaptic vesicles, which are specialized secretory organelles that store high concentrations of neurotransmitters. The rapid Ca2(+)-triggered fusion of synaptic vesicles is presumably mediated by specific proteins that must interact with Ca2+ and the phospholipid bilayer. We now report that the cytoplasmic domain of p65, a synaptic vesicle-specific protein that binds calmodulin contains an internally repeated sequence that is homologous to the regulatory C2-region of protein kinase C (PKC). The cytoplasmic domain of recombinant p65 binds acidic phospholipids with a specificity indicating an interaction of p65 with the hydrophobic core as well as the headgroups of the phospholipids. The binding specificity resembles PKC, except that p65 also binds calmodulin, placing the C2-regions in a context of potential Ca2(+)-regulation that is different from PKC. This is a novel homology between a cellular protein and the regulatory domain of protein kinase C. The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis. 相似文献