全文获取类型
收费全文 | 30044篇 |
免费 | 79篇 |
国内免费 | 83篇 |
专业分类
系统科学 | 248篇 |
丛书文集 | 536篇 |
教育与普及 | 72篇 |
理论与方法论 | 80篇 |
现状及发展 | 12737篇 |
研究方法 | 1178篇 |
综合类 | 14844篇 |
自然研究 | 511篇 |
出版年
2013年 | 154篇 |
2012年 | 362篇 |
2011年 | 904篇 |
2010年 | 145篇 |
2008年 | 435篇 |
2007年 | 529篇 |
2006年 | 519篇 |
2005年 | 536篇 |
2004年 | 537篇 |
2003年 | 534篇 |
2002年 | 458篇 |
2001年 | 971篇 |
2000年 | 976篇 |
1999年 | 588篇 |
1994年 | 328篇 |
1992年 | 588篇 |
1991年 | 496篇 |
1990年 | 545篇 |
1989年 | 469篇 |
1988年 | 500篇 |
1987年 | 492篇 |
1986年 | 489篇 |
1985年 | 675篇 |
1984年 | 517篇 |
1983年 | 429篇 |
1982年 | 351篇 |
1981年 | 371篇 |
1980年 | 454篇 |
1979年 | 946篇 |
1978年 | 800篇 |
1977年 | 731篇 |
1976年 | 617篇 |
1975年 | 662篇 |
1974年 | 827篇 |
1973年 | 709篇 |
1972年 | 763篇 |
1971年 | 891篇 |
1970年 | 1144篇 |
1969年 | 913篇 |
1968年 | 812篇 |
1967年 | 805篇 |
1966年 | 774篇 |
1965年 | 544篇 |
1959年 | 326篇 |
1958年 | 507篇 |
1957年 | 366篇 |
1956年 | 315篇 |
1955年 | 280篇 |
1954年 | 313篇 |
1948年 | 226篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
51.
Studies of intracellular traffic in yeast and mammalian systems have implicated members of the Rab family of small GTP-binding proteins as regulators of membrane fusion. We have used the patch clamp technique to measure exocytotic fusion events directly and investigate the role of GTP-binding proteins in regulating exocytosis in mast cells. Intracellular perfusion of mast cells with GTP-gamma S is sufficient to trigger complete exocytotic degranulation in the absence of other intracellular messengers. Here we show that GTP is a potent inhibitor of GTP-gamma S-induced degranulation, indicating that sustained activation of a GTP-binding protein is sufficient for membrane fusion. We have found that synthetic oligopeptides, corresponding to part of the effector domain of Rab3a, stimulate complete exocytotic degranulation, similar to that induced by GTP-gamma S. The response is selective for Rab3a sequence and is strictly dependent on Mg2+ and ATP. This suggests that sustained activation of a Rab3 protein causes exocytotic fusion. The peptide response can be accelerated by GDP-beta S, suggesting that Rab3a peptides compete with endogenous Rab3 proteins for a binding site on a target effector protein, which causes fusion on activation. 相似文献
52.
53.
54.
R. Poggioli A. V. Vergoni A. Bertolini 《Cellular and molecular life sciences : CMLS》1985,41(2):265-266
Summary Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.This work was supported in part by grants from Consiglio Nazionale delle Ricerche, and by Ministero della Pubblica Istruzione, Roma. 相似文献
55.
H R Brenner 《Nature》1985,317(6038):572-573
56.
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
57.
58.
Summary Traces of nor-adrenaline restore the vascular action of adrenaline altered in epinephrectomized dogs to the reaction of the normal animal. Therefore it is claimed that the adrenals discharge one or several substances into the blood stream, which are necessary for the usual peripheral vascular action of adrenaline. Further investigations are in progress. 相似文献
59.
Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
60.
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