全文获取类型
收费全文 | 1392篇 |
免费 | 4篇 |
国内免费 | 14篇 |
专业分类
系统科学 | 108篇 |
丛书文集 | 2篇 |
教育与普及 | 10篇 |
理论与方法论 | 27篇 |
现状及发展 | 203篇 |
研究方法 | 192篇 |
综合类 | 756篇 |
自然研究 | 112篇 |
出版年
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 12篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 10篇 |
2013年 | 34篇 |
2012年 | 106篇 |
2011年 | 224篇 |
2010年 | 38篇 |
2009年 | 7篇 |
2008年 | 95篇 |
2007年 | 96篇 |
2006年 | 85篇 |
2005年 | 120篇 |
2004年 | 109篇 |
2003年 | 100篇 |
2002年 | 93篇 |
2001年 | 16篇 |
2000年 | 14篇 |
1999年 | 19篇 |
1998年 | 13篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 14篇 |
1993年 | 5篇 |
1992年 | 20篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 10篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1974年 | 5篇 |
1972年 | 3篇 |
1967年 | 2篇 |
1966年 | 2篇 |
1965年 | 3篇 |
1958年 | 2篇 |
1957年 | 4篇 |
1956年 | 2篇 |
排序方式: 共有1410条查询结果,搜索用时 15 毫秒
41.
Burdon KP Macgregor S Hewitt AW Sharma S Chidlow G Mills RA Danoy P Casson R Viswanathan AC Liu JZ Landers J Henders AK Wood J Souzeau E Crawford A Leo P Wang JJ Rochtchina E Nyholt DR Martin NG Montgomery GW Mitchell P Brown MA Mackey DA Craig JE 《Nature genetics》2011,43(6):574-578
We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma. 相似文献
42.
Steinbusch LK Schwenk RW Ouwens DM Diamant M Glatz JF Luiken JJ 《Cellular and molecular life sciences : CMLS》2011,68(15):2525-2538
Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose
transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored
in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well
as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly
affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized
at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate
uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences
in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved
in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both
GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking
components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development
of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy. 相似文献
43.
This paper examines the information on future exchange rate movements provided by the doctrine of purchasing power parity (PPP). Previous research has studied this issue by analyzing the time-series properties of period-by-period levels of, or changes in, exchange rates. In contrast, the present study focuses on the durations of periods in which exchange rates deviate from their PPP levels. If PPP provides information about future exchange rate movements, these durations should exhibit positive duration dependence. That is, the probability of returning to PPP levels should increase as the period of deviation increases. Parametric hazard functions estimated using data from eighteen countries provide no evidence of positive duration dependence. These results are robust to alternative definitions of PPP and to alternative functional specifications. While exchange rates take prolonged swings away from their PPP levels and then eventually return, these movements apparently constitute Monte Carlo cycles in which, at any point in time, the probability of moving back toward PPP is the same as the probability of moving farther away. Thus, PPP provides no useful information on future exchange rate changes, a result consistent with market efficiency. 相似文献
44.
45.
46.
47.
48.
Thibault ST Singer MA Miyazaki WY Milash B Dompe NA Singh CM Buchholz R Demsky M Fawcett R Francis-Lang HL Ryner L Cheung LM Chong A Erickson C Fisher WW Greer K Hartouni SR Howie E Jakkula L Joo D Killpack K Laufer A Mazzotta J Smith RD Stevens LM Stuber C Tan LR Ventura R Woo A Zakrajsek I Zhao L Chen F Swimmer C Kopczynski C Duyk G Winberg ML Margolis J 《Nature genetics》2004,36(3):283-287
With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences. 相似文献
49.
L. Robert 《Cellular and molecular life sciences : CMLS》1981,37(10):1055-1058
Conclusion The brief summary of our present knowledge on the aging of intercellular matrix macromolecules shows the progress which has been made since the original important discovery of Verzár, but it also points out the very considerable gaps which still have to be filled by continued research efforts in this theoretically and practically important area. It is no secret to anyone that most of the disabling and killing diseases of advanced societies concern connective tissues: arteriosclerosis, diabetes, pulmonary obstructive lung diseases, osteoarticular diseases and cancer itself are all age-dependent, so-called aging diseases. The interaction between intercellular matrix and cancer cells plays an important role in the spreading of the tumors. For these other major diseases, the direct involvement of intercellular matrix is well documented. It is therefore hoped that a better grasp of the basic mechanisms involved in these diseases will help us to understand the difference between pathology and aging per se. 相似文献
50.
Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development 总被引:21,自引:0,他引:21
Golling G Amsterdam A Sun Z Antonelli M Maldonado E Chen W Burgess S Haldi M Artzt K Farrington S Lin SY Nissen RM Hopkins N 《Nature genetics》2002,31(2):135-140
To rapidly identify genes required for early vertebrate development, we are carrying out a large-scale, insertional mutagenesis screen in zebrafish, using mouse retroviral vectors as the mutagen. We will obtain mutations in 450 to 500 different genes--roughly 20% of the genes that can be mutated to produce a visible embryonic phenotype in this species--and will clone the majority of the mutated alleles. So far, we have isolated more than 500 insertional mutants. Here we describe the first 75 insertional mutants for which the disrupted genes have been identified. In agreement with chemical mutagenesis screens, approximately one-third of the mutants have developmental defects that affect primarily one or a small number of organs, body shape or swimming behavior; the rest of the mutants show more widespread or pleiotropic abnormalities. Many of the genes we identified have not been previously assigned a biological role in vivo. Roughly 20% of the mutants result from lesions in genes for which the biochemical and cellular function of the proteins they encode cannot be deduced with confidence, if at all, from their predicted amino-acid sequences. All of the genes have either orthologs or clearly related genes in human. These results provide an unbiased view of the genetic construction kit for a vertebrate embryo, reveal the diversity of genes required for vertebrate development and suggest that hundreds of genes of unknown biochemical function essential for vertebrate development have yet to be identified. 相似文献