全文获取类型
收费全文 | 30657篇 |
免费 | 68篇 |
国内免费 | 85篇 |
专业分类
系统科学 | 315篇 |
丛书文集 | 661篇 |
教育与普及 | 64篇 |
理论与方法论 | 117篇 |
现状及发展 | 14596篇 |
研究方法 | 1148篇 |
综合类 | 13608篇 |
自然研究 | 301篇 |
出版年
2012年 | 342篇 |
2011年 | 699篇 |
2010年 | 153篇 |
2009年 | 152篇 |
2008年 | 428篇 |
2007年 | 513篇 |
2006年 | 496篇 |
2005年 | 505篇 |
2004年 | 575篇 |
2003年 | 519篇 |
2002年 | 458篇 |
2001年 | 896篇 |
2000年 | 904篇 |
1999年 | 560篇 |
1992年 | 527篇 |
1991年 | 420篇 |
1990年 | 485篇 |
1989年 | 460篇 |
1988年 | 408篇 |
1987年 | 445篇 |
1986年 | 481篇 |
1985年 | 596篇 |
1984年 | 426篇 |
1983年 | 387篇 |
1982年 | 360篇 |
1981年 | 408篇 |
1980年 | 431篇 |
1979年 | 1029篇 |
1978年 | 839篇 |
1977年 | 822篇 |
1976年 | 625篇 |
1975年 | 701篇 |
1974年 | 1043篇 |
1973年 | 823篇 |
1972年 | 806篇 |
1971年 | 983篇 |
1970年 | 1231篇 |
1969年 | 1032篇 |
1968年 | 960篇 |
1967年 | 977篇 |
1966年 | 816篇 |
1965年 | 647篇 |
1964年 | 196篇 |
1959年 | 369篇 |
1958年 | 575篇 |
1957年 | 411篇 |
1956年 | 347篇 |
1955年 | 341篇 |
1954年 | 334篇 |
1948年 | 206篇 |
排序方式: 共有10000条查询结果,搜索用时 343 毫秒
41.
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
42.
43.
Sobacchi C Frattini A Guerrini MM Abinun M Pangrazio A Susani L Bredius R Mancini G Cant A Bishop N Grabowski P Del Fattore A Messina C Errigo G Coxon FP Scott DI Teti A Rogers MJ Vezzoni P Villa A Helfrich MH 《Nature genetics》2007,39(8):960-962
Autosomal recessive osteopetrosis is usually associated with normal or elevated numbers of nonfunctional osteoclasts. Here we report mutations in the gene encoding RANKL (receptor activator of nuclear factor-KB ligand) in six individuals with autosomal recessive osteopetrosis whose bone biopsy specimens lacked osteoclasts. These individuals did not show any obvious defects in immunological parameters and could not be cured by hematopoietic stem cell transplantation; however, exogenous RANKL induced formation of functional osteoclasts from their monocytes, suggesting that they could, theoretically, benefit from exogenous RANKL administration. 相似文献
44.
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
45.
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
46.
Gösta Lindeberg 《Cellular and molecular life sciences : CMLS》1948,4(12):476-477
Zusammenfassung Es wurde die Zugkraft nasser Flachsfasern nach Behandlung mit verschiedenen Chemikalien geprüft. Es wurde gefunden, daß die Mittellamelle der Flachsfaser verschiedene miteinander verbundene Systeme enthält, nämlich Pektin, Lignin und eine im Oxalat unlös iche alkaliempfindliche Komponente. 相似文献
47.
煤矸石空心砖是一种新型环保墙体材料,符合国家及山西省出台的限制生产和使用实心黏土砖,鼓励发展新型建筑材料的政策。利用煤矸石制造的空心砖可以作为保温材料,既可节约建筑能耗,又可节约土地资源,减少环境污染。煤矸石空心砖同黏土实心砖相比,具有高强、轻质、隔音、隔热、保温、防震等优点,市场前景良好。 相似文献
48.
49.
Growth hormone signal transduction 总被引:1,自引:0,他引:1
Growth hormone (GH) promotes animal growth by stimulating bone and cartilage cell proliferation, and influences carbohydrate and lipid metabolism. Some of these effects are brought about indirectly via somatomedin induction in hepatocytes, others by acting directly on the target cells. In either case, GH first binds to specific receptors on cells to trigger a sequence of biochemical events culminating in a biological response. Recently much has been learnt about the molecular structure of GH receptor, its binding to ligand, and the ensuing signal transduction events. 相似文献
50.
DNA fingerprinting transforms the art of cell authentication. 总被引:4,自引:0,他引:4
The increasing diversity of new cell cultures is seriously stretching the capabilities of traditional methods of identification. DNA fingerprinting is set to play an important role in increasing confidence in the authenticity of cultures in research and industry. 相似文献