全文获取类型
收费全文 | 27957篇 |
免费 | 91篇 |
国内免费 | 160篇 |
专业分类
系统科学 | 150篇 |
丛书文集 | 199篇 |
教育与普及 | 92篇 |
理论与方法论 | 112篇 |
现状及发展 | 12238篇 |
研究方法 | 1264篇 |
综合类 | 13780篇 |
自然研究 | 373篇 |
出版年
2012年 | 489篇 |
2011年 | 845篇 |
2010年 | 202篇 |
2008年 | 583篇 |
2007年 | 669篇 |
2006年 | 627篇 |
2005年 | 670篇 |
2004年 | 687篇 |
2003年 | 597篇 |
2002年 | 677篇 |
2001年 | 776篇 |
2000年 | 797篇 |
1999年 | 533篇 |
1994年 | 347篇 |
1992年 | 437篇 |
1991年 | 361篇 |
1990年 | 437篇 |
1989年 | 397篇 |
1988年 | 408篇 |
1987年 | 428篇 |
1986年 | 419篇 |
1985年 | 525篇 |
1984年 | 401篇 |
1983年 | 397篇 |
1982年 | 370篇 |
1981年 | 362篇 |
1980年 | 375篇 |
1979年 | 859篇 |
1978年 | 703篇 |
1977年 | 605篇 |
1976年 | 551篇 |
1975年 | 598篇 |
1974年 | 689篇 |
1973年 | 604篇 |
1972年 | 631篇 |
1971年 | 810篇 |
1970年 | 913篇 |
1969年 | 726篇 |
1968年 | 786篇 |
1967年 | 706篇 |
1966年 | 609篇 |
1965年 | 444篇 |
1964年 | 217篇 |
1959年 | 235篇 |
1958年 | 461篇 |
1957年 | 337篇 |
1956年 | 285篇 |
1955年 | 270篇 |
1954年 | 267篇 |
1948年 | 221篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
491.
A variety of viral-based and immune cell therapies have been proposed for use in the treatment of cancer. One possible approach
to improve the effectiveness of these biological agents may be to combine them such that we can take advantage of natural
immune cell-pathogen relationships. Here we discuss these potential approaches with particular emphasis on the use of immune
cells as carrier vehicles to deliver viral therapies to the tumor.
Received 15 December 2006; received after revision 28 January 2007; accepted 5 March 2007 相似文献
492.
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
493.
Houlden H Johnson J Gardner-Thorpe C Lashley T Hernandez D Worth P Singleton AB Hilton DA Holton J Revesz T Davis MB Giunti P Giunti P Wood NW 《Nature genetics》2007,39(12):1434-1436
The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration. 相似文献
494.
Romeo S Pennacchio LA Fu Y Boerwinkle E Tybjaerg-Hansen A Hobbs HH Cohen JC 《Nature genetics》2007,39(4):513-516
Resequencing genes provides the opportunity to assess the full spectrum of variants that influence complex traits. Here we report the first application of resequencing to a large population (n = 3,551) to examine the role of the adipokine ANGPTL4 in lipid metabolism. Nonsynonymous variants in ANGPTL4 were more prevalent in individuals with triglyceride levels in the lowest quartile than in individuals with levels in the highest quartile (P = 0.016). One variant (E40K), present in approximately 3% of European Americans, was associated with significantly lower plasma levels of triglyceride and higher levels of high-density lipoprotein cholesterol in European Americans from the Atherosclerosis Risk in Communities Study and in Danes from the Copenhagen City Heart Study. The ratio of nonsynonymous to synonymous variants was higher in European Americans than in African Americans (4:1 versus 1.3:1), suggesting population-specific relaxation of purifying selection. Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history. 相似文献
495.
496.
497.
Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis 总被引:4,自引:0,他引:4
498.
Dina C Meyre D Gallina S Durand E Körner A Jacobson P Carlsson LM Kiess W Vatin V Lecoeur C Delplanque J Vaillant E Pattou F Ruiz J Weill J Levy-Marchal C Horber F Potoczna N Hercberg S Le Stunff C Bougnères P Kovacs P Marre M Balkau B Cauchi S Chèvre JC Froguel P 《Nature genetics》2007,39(6):724-726
We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses. 相似文献
499.
Tissue-specific and reversible RNA interference in transgenic mice 总被引:11,自引:0,他引:11
Dickins RA McJunkin K Hernando E Premsrirut PK Krizhanovsky V Burgess DJ Kim SY Cordon-Cardo C Zender L Hannon GJ Lowe SW 《Nature genetics》2007,39(7):914-921
Genetically engineered mice provide powerful tools for understanding mammalian gene function. These models traditionally rely on gene overexpression from transgenes or targeted, irreversible gene mutation. By adapting the tetracycline (tet)-responsive system previously used for gene overexpression, we have developed a simple transgenic system to reversibly control endogenous gene expression using RNA interference (RNAi) in mice. Transgenic mice harboring a tet-responsive RNA polymerase II promoter driving a microRNA-based short hairpin RNA targeting the tumor suppressor Trp53 reversibly express short hairpin RNA when crossed with existing mouse strains expressing general or tissue-specific 'tet-on' or 'tet-off' transactivators. Reversible Trp53 knockdown can be achieved in several tissues, and restoring Trp53 expression in lymphomas whose development is promoted by Trp53 knockdown leads to tumor regression. By leaving the target gene unaltered, this approach permits tissue-specific, reversible regulation of endogenous gene expression in vivo, with potential broad application in basic biology and drug target validation. 相似文献
500.