全文获取类型
收费全文 | 40566篇 |
免费 | 119篇 |
国内免费 | 200篇 |
专业分类
系统科学 | 380篇 |
丛书文集 | 875篇 |
教育与普及 | 76篇 |
理论与方法论 | 143篇 |
现状及发展 | 19154篇 |
研究方法 | 1575篇 |
综合类 | 18158篇 |
自然研究 | 524篇 |
出版年
2013年 | 294篇 |
2012年 | 512篇 |
2011年 | 1086篇 |
2010年 | 232篇 |
2008年 | 674篇 |
2007年 | 798篇 |
2006年 | 734篇 |
2005年 | 720篇 |
2004年 | 712篇 |
2003年 | 713篇 |
2002年 | 654篇 |
2001年 | 1279篇 |
2000年 | 1215篇 |
1999年 | 783篇 |
1992年 | 781篇 |
1991年 | 563篇 |
1990年 | 667篇 |
1989年 | 656篇 |
1988年 | 619篇 |
1987年 | 686篇 |
1986年 | 663篇 |
1985年 | 803篇 |
1984年 | 630篇 |
1983年 | 508篇 |
1982年 | 478篇 |
1981年 | 531篇 |
1980年 | 627篇 |
1979年 | 1272篇 |
1978年 | 1060篇 |
1977年 | 1062篇 |
1976年 | 856篇 |
1975年 | 885篇 |
1974年 | 1264篇 |
1973年 | 1073篇 |
1972年 | 1069篇 |
1971年 | 1205篇 |
1970年 | 1579篇 |
1969年 | 1260篇 |
1968年 | 1200篇 |
1967年 | 1216篇 |
1966年 | 1033篇 |
1965年 | 732篇 |
1964年 | 218篇 |
1959年 | 406篇 |
1958年 | 682篇 |
1957年 | 451篇 |
1956年 | 411篇 |
1955年 | 389篇 |
1954年 | 365篇 |
1948年 | 229篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
621.
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
622.
de Wit PJ 《Cellular and molecular life sciences : CMLS》2007,64(21):2726-2732
Plants have an innate immunity system to defend themselves against pathogens. With the primary immune system, plants recognize
microbe-associated molecular patterns (MAMPs) of potential pathogens through pattern recognition receptors (PRRs) that mediate
a basal defense response. Plant pathogens suppress this basal defense response by means of effectors that enable them to cause
disease. With the secondary immune system, plants have gained the ability to recognize effector-induced perturbations of host
targets through resistance proteins (RPs) that mediate a strong local defense response that stops pathogen growth. Both primary
and secondary immune responses in plants depend on germ line-encoded PRRs and RPs. During induction of local immune responses,
systemic immune responses also become activated, which predispose plants to become more resistant to subsequent pathogen attacks.
This review gives an update on recent findings that have enhanced our understanding of plant innate immunity and the arms
race between plants and their pathogens.
Received 24 June 2007; received after revision 18 July 2007; accepted 15 August 2007 相似文献
623.
Hunt MC Greene S Hultenby K Svensson LT Engberg S Alexson SE 《Cellular and molecular life sciences : CMLS》2007,64(12):1558-1570
Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of acyl-CoAs to free fatty acids and coenzyme A. Recent studies have
demonstrated that one gene named Acot7, reported to be mainly expressed in brain and testis, is transcribed in several different isoforms by alternative usage of
first exons. Strongly decreased levels of ACOT7 activity and protein in both mitochondria and cytosol was reported in patients
diagnosed with fatty acid oxidation defects, linking ACOT7 function to regulation of fatty acid oxidation in other tissues.
In this study, we have identified five possible first exons in mouse Acot7 (Acot7a–e) and show that all five first exons are transcribed in a tissue-specific manner. Taken together, these data show that the
Acot7 gene is expressed as multiple isoforms in a tissue-specific manner, and that expression in tissues other than brain and testis
is likely to play important roles in fatty acid metabolism.
Received 5 February 2007: received after revision 3 April 2007; accepted 19 April 2007 相似文献
624.
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
625.
Dhar-Chowdhury P Malester B Rajacic P Coetzee WA 《Cellular and molecular life sciences : CMLS》2007,64(23):3069-3083
Glycolysis is an evolutionary conserved metabolic pathway that provides small amounts of energy in the form of ATP when compared
to other pathways such as oxidative phosphorylation or fatty acid oxidation. The ATP levels inside metabolically active cells
are not constant and the local ATP level will depend on the site of production as well as the respective rates of ATP production,
diffusion and consumption. Membrane ion transporters (pumps, exchangers and channels) are located at sites distal to the major
sources of ATP formation (the mitochondria). We review evidence that the glycolytic complex is associated with membranes;
both at the plasmalemma and with membranes of the endo/sarcoplasmic reticular network. We examine the evidence for the concept
that many of the ion transporters are regulated preferentially by the glycolytic process. These include the Na+/K+-ATPase, the H+-ATPase, various types of Ca2+-ATPases, the Na+/H+ exchanger, the ATP-sensitive K+ channel, cation channels, Na+ channels, Ca2+ channels and other channels involved in intracellular Ca2+ homeostasis. Regulation of these pumps, exchangers and ion channels by the glycolytic process has important consequences
in a variety of physiological and pathophysiological processes, and a better understanding of this mode of regulation may
have important consequences for developing future strategies in combating disease and developing novel therapeutic approaches.
Received 20 July 2007; received after revision 30 July 2007; accepted 17 August 2007 相似文献
626.
Edouard T Montagner A Dance M Conte F Yart A Parfait B Tauber M Salles JP Raynal P 《Cellular and molecular life sciences : CMLS》2007,64(13):1585-1590
Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes.
Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by
mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis
of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1,
Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated
by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative
effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK
activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the
possibility that LS mutations may not simply exhibit dominant negative activity.
Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007 相似文献
627.
628.
629.
Péterfy M Ben-Zeev O Mao HZ Weissglas-Volkov D Aouizerat BE Pullinger CR Frost PH Kane JP Malloy MJ Reue K Pajukanta P Doolittle MH 《Nature genetics》2007,39(12):1483-1487
Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia. 相似文献
630.