全文获取类型
收费全文 | 38876篇 |
免费 | 68篇 |
国内免费 | 107篇 |
专业分类
系统科学 | 184篇 |
丛书文集 | 779篇 |
教育与普及 | 99篇 |
理论与方法论 | 233篇 |
现状及发展 | 17191篇 |
研究方法 | 1540篇 |
综合类 | 18527篇 |
自然研究 | 498篇 |
出版年
2013年 | 245篇 |
2012年 | 523篇 |
2011年 | 1046篇 |
2010年 | 232篇 |
2008年 | 648篇 |
2007年 | 668篇 |
2006年 | 702篇 |
2005年 | 716篇 |
2004年 | 637篇 |
2003年 | 691篇 |
2002年 | 666篇 |
2001年 | 1148篇 |
2000年 | 1055篇 |
1999年 | 731篇 |
1992年 | 696篇 |
1991年 | 557篇 |
1990年 | 602篇 |
1989年 | 595篇 |
1988年 | 599篇 |
1987年 | 612篇 |
1986年 | 578篇 |
1985年 | 737篇 |
1984年 | 584篇 |
1983年 | 494篇 |
1982年 | 444篇 |
1981年 | 434篇 |
1980年 | 572篇 |
1979年 | 1214篇 |
1978年 | 1031篇 |
1977年 | 1020篇 |
1976年 | 757篇 |
1975年 | 823篇 |
1974年 | 1127篇 |
1973年 | 1008篇 |
1972年 | 1066篇 |
1971年 | 1256篇 |
1970年 | 1631篇 |
1969年 | 1259篇 |
1968年 | 1211篇 |
1967年 | 1239篇 |
1966年 | 1059篇 |
1965年 | 754篇 |
1964年 | 191篇 |
1959年 | 447篇 |
1958年 | 683篇 |
1957年 | 541篇 |
1956年 | 456篇 |
1955年 | 397篇 |
1954年 | 424篇 |
1948年 | 269篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
821.
McTaggart SJ 《Cellular and molecular life sciences : CMLS》2006,63(3):255-267
Isoprenoids are synthesized in all living organisms and are incorporated into diverse classes of end-products that participate
in a multitude of cellular processes relating to cell growth, differentiation, cytoskeletal function and vesicle trafficking.
In humans, the non-sterol isoprenoids, farnesyl pyrophosphate and geranylgeranyl-pyrophosphate, are synthesized via the mevalonate
pathway and are covalently added to members of the small G protein superfamily. Isoprenylated proteins have key roles in membrane
attachment and protein functionality, have been shown to have a central role in some cancers and are likely also to be involved
in the pathogenesis and progression of atherosclerosis and Alzheimer disease. This review details current knowledge on the
biosynthesis of isoprenoids, their incorporation into proteins by the process known as prenylation and the complex regulatory
network that controls these proteins. An improved understanding of these processe is likely to lead to the development of
novel therapies that will have important implications for human health and disease.
Received 5 July 2005; received after revision 17 October 2005; accepted 22 October 2005 相似文献
822.
823.
Amundadottir LT Sulem P Gudmundsson J Helgason A Baker A Agnarsson BA Sigurdsson A Benediktsdottir KR Cazier JB Sainz J Jakobsdottir M Kostic J Magnusdottir DN Ghosh S Agnarsson K Birgisdottir B Le Roux L Olafsdottir A Blondal T Andresdottir M Gretarsdottir OS Bergthorsson JT Gudbjartsson D Gylfason A Thorleifsson G Manolescu A Kristjansson K Geirsson G Isaksson H Douglas J Johansson JE Bälter K Wiklund F Montie JE Yu X Suarez BK Ober C Cooney KA Gronberg H Catalona WJ Einarsson GV 《Nature genetics》2006,38(6):652-658
With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry. 相似文献
824.
Sayer JA Otto EA O'Toole JF Nurnberg G Kennedy MA Becker C Hennies HC Helou J Attanasio M Fausett BV Utsch B Khanna H Liu Y Drummond I Kawakami I Kusakabe T Tsuda M Ma L Lee H Larson RG Allen SJ Wilkinson CJ Nigg EA Shou C Lillo C Williams DS Hoppe B Kemper MJ Neuhaus T Parisi MA Glass IA Petry M Kispert A Gloy J Ganner A Walz G Zhu X Goldman D Nurnberg P Swaroop A Leroux MR Hildebrandt F 《Nature genetics》2006,38(6):674-681
825.
826.
827.
Recent experience with several high-profile drugs demonstrates the great challenges in developing effective and safe therapeutics. A complementary approach to the popular paradigm of disease genetics is based on inherited factors that reduce the incidence and severity of disease among individuals who are genetically predisposed to disease. We propose testing specifically for modifier genes and protective alleles among at-risk individuals and studying the efficacy of therapeutics based on the genetics of health. 相似文献
828.
Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration 总被引:12,自引:0,他引:12
Maller J George S Purcell S Fagerness J Altshuler D Daly MJ Seddon JM 《Nature genetics》2006,38(9):1055-1059
Age-related macular degeneration (AMD) is a common, late-onset disease with seemingly typical complexity: recurrence ratios for siblings of an affected individual are three- to sixfold higher than in the general population, and family-based analysis has resulted in only modestly significant evidence for linkage. In a case-control study drawn from a US-based population of European descent, we have identified a previously unrecognized common, noncoding variant in CFH, the gene encoding complement factor H, that substantially increases the influence of this locus on AMD, and we have strongly replicated the associations of four other previously reported common alleles in three genes (P values ranging from 10(-6) to 10(-70)). Despite excellent power to detect epistasis, we observed purely additive accumulation of risk from alleles at these genes. We found no differences in association of these loci with major phenotypic categories of advanced AMD. Genotypes at these five common SNPs define a broad spectrum of interindividual disease risk and explain about half of the classical sibling risk of AMD in our study population. 相似文献
829.
Richardson RJ Dixon J Malhotra S Hardman MJ Knowles L Boot-Handford RP Shore P Whitmarsh A Dixon MJ 《Nature genetics》2006,38(11):1329-1334
The epidermis is a highly organized structure, the integrity of which is central to the protection of an organism. Development and subsequent maintenance of this tissue depends critically on the intricate balance between proliferation and differentiation of a resident stem cell population; however, the signals controlling the proliferation-differentiation switch in vivo remain elusive. Here, we show that mice carrying a homozygous missense mutation in interferon regulatory factor 6 (Irf6), the homolog of the gene mutated in the human congenital disorders Van der Woude syndrome and popliteal pterygium syndrome, have a hyperproliferative epidermis that fails to undergo terminal differentiation, resulting in soft tissue fusions. We further demonstrate that mice that are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show similar defects of keratinizing epithelia. Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process. 相似文献
830.
Aggressive behavior is pervasive throughout the animal kingdom, and yet very little is known about its molecular underpinnings. To address this problem, we have developed a population-based selection procedure to increase aggression in Drosophila melanogaster. We measured changes in aggressive behavior in the selected subpopulations with a new two-male arena assay. In only ten generations of selection, the aggressive lines became markedly more aggressive than the neutral lines. After 21 generations, the fighting index increased more than 30-fold. Using microarray analysis, we identified genes with differing expression levels in the aggressive and neutral lines as candidates for this strong behavioral selection response. We tested a small set of these genes through mutant analysis and found that one significantly increased fighting frequency. These results suggest that selection for increases in aggression can be used to molecularly dissect this behavior. 相似文献