全文获取类型
收费全文 | 59707篇 |
免费 | 266篇 |
国内免费 | 543篇 |
专业分类
系统科学 | 1238篇 |
丛书文集 | 566篇 |
教育与普及 | 285篇 |
理论与方法论 | 530篇 |
现状及发展 | 32866篇 |
研究方法 | 879篇 |
综合类 | 21963篇 |
自然研究 | 2189篇 |
出版年
2013年 | 803篇 |
2012年 | 621篇 |
2011年 | 2666篇 |
2009年 | 597篇 |
2008年 | 822篇 |
2007年 | 935篇 |
2006年 | 1047篇 |
2005年 | 1198篇 |
2004年 | 2294篇 |
2003年 | 1925篇 |
2002年 | 1574篇 |
2001年 | 1539篇 |
2000年 | 1098篇 |
1999年 | 1030篇 |
1998年 | 644篇 |
1997年 | 773篇 |
1996年 | 532篇 |
1994年 | 684篇 |
1993年 | 695篇 |
1992年 | 967篇 |
1991年 | 858篇 |
1990年 | 941篇 |
1989年 | 730篇 |
1988年 | 727篇 |
1987年 | 726篇 |
1986年 | 772篇 |
1985年 | 988篇 |
1984年 | 835篇 |
1983年 | 720篇 |
1982年 | 811篇 |
1981年 | 848篇 |
1980年 | 961篇 |
1979年 | 1511篇 |
1978年 | 1355篇 |
1977年 | 1323篇 |
1976年 | 1176篇 |
1975年 | 1187篇 |
1974年 | 1120篇 |
1973年 | 1323篇 |
1972年 | 1400篇 |
1971年 | 1445篇 |
1970年 | 1670篇 |
1969年 | 1441篇 |
1968年 | 1335篇 |
1967年 | 1253篇 |
1966年 | 1076篇 |
1965年 | 850篇 |
1959年 | 519篇 |
1958年 | 679篇 |
1957年 | 574篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
931.
932.
The development and maturation of an oligodendroglial cell is comprised of three intimately related processes that include proliferation, differentiation, and myelination. Here we review how proliferation and differentiation are controlled by distinct molecular mechanisms and discuss whether differentiation is merely a default of inhibited proliferation. We then address whether differentiation and myelination can be uncoupled in a similar manner. This task is particularly challenging because an oligodendrocyte cannot myelinate without first differentiating, and these processes are therefore not mutually exclusive. Is it solely the presence of the axon that distinguishes a differentiated oligodendrocyte from a myelinating one? Uncoupling these two processes requires identifying specific signals that regulate myelination without affecting the differentiation process. We will review current understanding of the relationship between differentiation and myelination and discuss whether these two processes can truly be uncoupled. 相似文献
933.
Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune system is peptidoglycan, one of
the most abundant constituents of the bacterial cell wall. Insects use peptidoglycan recognition proteins to detect peptidoglycan
and to activate innate immune responses. Such specialized peptidoglycan receptors appear to have evolved from phage enzymes
that hydrolyze bacterial cell walls. They are able to bind specific peptidoglycan molecules with distinct chemical moieties
and activate innate immune pathways by interacting with other signaling proteins. Recent X-ray crystallographic studies of
the peptidoglycan recognition proteins LCa, and LCx bound to peptidoglycan have provided structural insights into recognition
of peptidoglycan and activation of innate immunity in insects.
Received 28 December 2006; received after revision 2 February 2007; accepted 21 February 2007 相似文献
934.
The study of candidate genes over the past three decades has yielded notable successes in common-disease genetics. During
this time, however, interpretation of genetic association studies has been hampered by the use of clinical cohorts of inadequate
power and insufficient information on genetic variation in candidate genes. The unavailability of highthroughput and low-cost
genotyping technologies has also limited the scope of complex-disease genetic studies. More recently, however, the sequencing
and characterization of variation within the human genome has revolutionized genetic studies and enabled full genome-wide
scans for genes associated with disease. The identification of disease-associated (causative) genes has illuminated disease
mechanisms. The translation of this knowledge into direct clinical benefit in diagnosis, prognosis and therapy for an individual’s
disease still remains a challenge.
Received 11 September 2006; received after revision 17 December 2006; accepted 18 January 2007 相似文献
935.
Larrucea S Butta N Rodriguez RB Alonso-Martin S Arias-Salgado EG Ayuso MS Parrilla R 《Cellular and molecular life sciences : CMLS》2007,64(22):2965-2974
Podocalyxin (PODXL) is a mucin protein of the CD34 family expressed in kidney glomerular podocytes, vascular endothelium,
progenitor bone marrow and tumor cells. It is assumed that PODXL plays an anti-adherent role in kidney podocytes. CHO cells
stably expressing human PODXL (CHO-PODXL) or human tumor cells (Tera-1) inherently expressing PODXL showed increased adherence
to platelets. The adherence of cells was inhibited (70%) by blockers of platelet P-selectin, prevented by the soluble ectodomain
of human PODXL (PODXL-Δ) or by the arginine-glycine-aspartate (RGDS) peptide and partially impeded by inhibition of integrin
αVβ3/αVβ5, suggesting a coordinated action of P-selectin and integrins. Colocalization of platelet P-selectin and PODXL expressed
on CHO cells was demonstrated by confocal immunofluorescence. No adherence to platelets was observed when PODXL was expressed
in glycomutant CHO cells deficient in sialic acid.
Received 14 August 2007; received after revision 12 September 2007; accepted 13 September 2007 相似文献
936.
Advances in our understanding of cardiac development have fuelled research into cellular approaches to myocardial repair of
the damaged heart. In this collection of reviews we present recent advances into the basic mechanisms of heart development
and the resident and non-resident progenitor cell populations that are currently being investigated as potential mediators
of cardiac repair. Together these reviews illustrate that despite our current knowledge about how the heart is constructed,
caution and much more research in this exciting field is essential. The current momentum to evaluate the potential for cardiac
repair will in turn accelerate research into fundamental aspects of myocardial biology. 相似文献
937.
Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer 总被引:2,自引:2,他引:0
The fraction of pyruvate dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase
isozymes (PDK1, PDK2, PDK3 and PDK4). Via binding to the inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2
60mer), PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited
by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal
regulatory (R) domain. Via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2,
which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation. Activation of PDC by synthetic PDK
inhibitors binding at the pyruvate or lipoyl binding sites decreased damage during heart ischemia and lowered blood glucose
in insulin-resistant animals. PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate.
Received 25 August 2006; received after revision 20 November 2006; accepted 20 December 2006 相似文献
938.
Komen JC Distelmaier F Koopman WJ Wanders RJ Smeitink J Willems PH 《Cellular and molecular life sciences : CMLS》2007,64(24):3271-3281
Refsum disease is a rare, inherited neurodegenerative disorder characterized by accumulation of the dietary branched-chain
fatty acid phytanic acid in plasma and tissues caused by a defect in the alphaoxidation pathway. The accumulation of phytanic
acid is believed to be the main pathophysiological cause of the disease. However, the exact mechanism(s) by which phytanic
acid exerts its toxicity have not been resolved. In this study, the effect of phytanic acid on mitochondrial respiration was
investigated. The results show that in digitonin-permeabilized fibroblasts, phytanic acid decreases ATP synthesis, whereas
substrate oxidation per se is not affected. Importantly, studies in intact fibroblasts revealed that phytanic acid decreases both the mitochondrial
membrane potential and NAD(P)H autofluorescence. Taken together, the results described here show that unesterified phytanic
acid exerts its toxic effect mainly through its protonophoric action, at least in human skin fibroblasts.
Received 4 August 2007; received after revision 26 September 2007; accepted 10 October 2007
J. C. Komen, F. Distelmaier: These authors contributed equally to this work. 相似文献
939.
Samuel CS Hewitson TD Unemori EN Tang ML 《Cellular and molecular life sciences : CMLS》2007,64(12):1539-1557
The peptide hormone relaxin is emerging as a multi-functional factor in a broad range of target tissues including several
non-reproductive organs, in addition to its historical role as a hormone of pregnancy. This review discusses the evidence
that collectively demonstrates the many diverse and vital roles of relaxin: the homeostatic role of endogenous relaxin in
mammalian pregnancy and ageing; its gender-related effects; the therapeutic effects of relaxin in the treatment of fibrosis,
inflammation, cardioprotection, vasodilation and wound healing (angiogenesis) amongst other pathophysiological conditions,
and its potential mechanism of action. Furthermore, translational issues using experimental models (to humans) and its use
in various clinical trials, are described, each with important lessons for the design of future trials involving relaxin.
The diverse physiological and pathological roles for relaxin have led to the search for its significance in humans and highlight
its potential as a drug of the future.
Received 12 December 2006; received after revision 12 February 2007; accepted 15 March 2007 相似文献
940.