全文获取类型
收费全文 | 609篇 |
免费 | 0篇 |
国内免费 | 8篇 |
专业分类
系统科学 | 6篇 |
教育与普及 | 1篇 |
理论与方法论 | 4篇 |
现状及发展 | 58篇 |
研究方法 | 134篇 |
综合类 | 383篇 |
自然研究 | 31篇 |
出版年
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 10篇 |
2016年 | 6篇 |
2015年 | 7篇 |
2014年 | 8篇 |
2013年 | 9篇 |
2012年 | 57篇 |
2011年 | 103篇 |
2010年 | 23篇 |
2009年 | 7篇 |
2008年 | 54篇 |
2007年 | 67篇 |
2006年 | 46篇 |
2005年 | 59篇 |
2004年 | 50篇 |
2003年 | 39篇 |
2002年 | 40篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1995年 | 2篇 |
1992年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1978年 | 4篇 |
排序方式: 共有617条查询结果,搜索用时 15 毫秒
91.
Lessons from natural molecules 总被引:1,自引:0,他引:1
Natural products have inspired chemists and physicians for millennia. Their rich structural diversity and complexity has prompted synthetic chemists to produce them in the laboratory, often with therapeutic applications in mind, and many drugs used today are natural products or natural-product derivatives. Recent years have seen considerable advances in our understanding of natural-product biosynthesis. Coupled with improvements in approaches for natural-product isolation, characterization and synthesis, these could be opening the door to a new era in the investigation of natural products in academia and industry. 相似文献
92.
93.
94.
95.
The mammalian immune system has an extraordinary potential for making receptors that sense and neutralize any chemical entity entering the body. Inevitably, some of these receptors recognize components of our own body, and so cellular mechanisms have evolved to control the activity of these 'forbidden' receptors and achieve immunological self tolerance. Many of the genes and proteins involved are conserved between humans and other mammals. This provides the bridge between clinical studies and mechanisms defined in experimental animals to understand how sets of gene products coordinate self-tolerance mechanisms and how defects in these controls lead to autoimmune disease. 相似文献
96.
97.
98.
Suhre K Shin SY Petersen AK Mohney RP Meredith D Wägele B Altmaier E;CARDIoGRAM Deloukas P Erdmann J Grundberg E Hammond CJ de Angelis MH Kastenmüller G Köttgen A Kronenberg F Mangino M Meisinger C Meitinger T Mewes HW Milburn MV Prehn C Raffler J Ried JS Römisch-Margl W Samani NJ Small KS Wichmann HE Zhai G Illig T Spector TD Adamski J Soranzo N Gieger C 《Nature》2011,477(7362):54-60
Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research. 相似文献
99.
Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms 总被引:39,自引:0,他引:39
Barouch LA Harrison RW Skaf MW Rosas GO Cappola TP Kobeissi ZA Hobai IA Lemmon CA Burnett AL O'Rourke B Rodriguez ER Huang PL Lima JA Berkowitz DE Hare JM 《Nature》2002,416(6878):337-339
Subcellular localization of nitric oxide (NO) synthases with effector molecules is an important regulatory mechanism for NO signalling. In the heart, NO inhibits L-type Ca2+ channels but stimulates sarcoplasmic reticulum (SR) Ca2+ release, leading to variable effects on myocardial contractility. Here we show that spatial confinement of specific NO synthase isoforms regulates this process. Endothelial NO synthase (NOS3) localizes to caveolae, where compartmentalization with beta-adrenergic receptors and L-type Ca2+ channels allows NO to inhibit beta-adrenergic-induced inotropy. Neuronal NO synthase (NOS1), however, is targeted to cardiac SR. NO stimulation of SR Ca2+ release via the ryanodine receptor (RyR) in vitro, suggests that NOS1 has an opposite, facilitative effect on contractility. We demonstrate that NOS1-deficient mice have suppressed inotropic response, whereas NOS3-deficient mice have enhanced contractility, owing to corresponding changes in SR Ca2+ release. Both NOS1-/- and NOS3-/- mice develop age-related hypertrophy, although only NOS3-/- mice are hypertensive. NOS1/3-/- double knockout mice have suppressed beta-adrenergic responses and an additive phenotype of marked ventricular remodelling. Thus, NOS1 and NOS3 mediate independent, and in some cases opposite, effects on cardiac structure and function. 相似文献
100.
Christopher Hollings 《Archive for History of Exact Sciences》2009,63(5):497-536
In the history of mathematics, the algebraic theory of semigroups is a relative new-comer, with the theory proper developing
only in the second half of the twentieth century. Before this, however, much groundwork was laid by researchers arriving at
the study of semigroups from the directions of both group and ring theory. In this paper, we will trace some major strands
in the early development of the algebraic theory of semigroups. We will begin with the aspects of the theory which were directly
inspired by, and were analogous to, existing results for both groups and rings, before moving on to consider the first independent
theorems on semigroups: theorems with no group or ring analogues.
Dedicated to the memory of Professor W. Douglas Munn.
This article was begun when the author was an EPSRC-funded research student at the University of York, UK, and completed at
CAUL under FCT post-doctoral research grant SFRH/BPD/34698/2007. 相似文献