全文获取类型
收费全文 | 149篇 |
免费 | 0篇 |
国内免费 | 7篇 |
专业分类
系统科学 | 3篇 |
现状及发展 | 51篇 |
研究方法 | 14篇 |
综合类 | 87篇 |
自然研究 | 1篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2018年 | 3篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 3篇 |
2013年 | 1篇 |
2012年 | 13篇 |
2011年 | 15篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 4篇 |
2007年 | 11篇 |
2006年 | 9篇 |
2005年 | 6篇 |
2004年 | 6篇 |
2003年 | 9篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 3篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 7篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 11篇 |
1971年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有156条查询结果,搜索用时 15 毫秒
101.
Ellinor PT Lunetta KL Albert CM Glazer NL Ritchie MD Smith AV Arking DE Müller-Nurasyid M Krijthe BP Lubitz SA Bis JC Chung MK Dörr M Ozaki K Roberts JD Smith JG Pfeufer A Sinner MF Lohman K Ding J Smith NL Smith JD Rienstra M Rice KM Van Wagoner DR Magnani JW Wakili R Clauss S Rotter JI Steinbeck G Launer LJ Davies RW Borkovich M Harris TB Lin H Völker U Völzke H Milan DJ Hofman A Boerwinkle E Chen LY Soliman EZ Voight BF Li G Chakravarti A Kubo M Tedrow UB Rose LM Ridker PM Conen D Tsunoda T 《Nature genetics》2012,44(6):670-675
102.
Vijaykrishna D Smith GJ Pybus OG Zhu H Bhatt S Poon LL Riley S Bahl J Ma SK Cheung CL Perera RA Chen H Shortridge KF Webby RJ Webster RG Guan Y Peiris JS 《Nature》2011,473(7348):519-522
Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12?years of systematic surveillance in this region, supplemented with data stretching back 34?years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans. 相似文献
103.
Wang Z Klipfell E Bennett BJ Koeth R Levison BS Dugar B Feldstein AE Britt EB Fu X Chung YM Wu Y Schauer P Smith JD Allayee H Tang WH DiDonato JA Lusis AJ Hazen SL 《Nature》2011,472(7341):57-63
Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine--choline, trimethylamine N-oxide (TMAO) and betaine--were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease. 相似文献
104.
Transfer function or distributed lag models are commonly used in forecasting. The stability of a constant‐coefficient transfer function model, however, may become an issue for many economic variables due in part to the recent advance in technology and improvement in efficiency in data collection and processing. In this paper, we propose a simple functional‐coefficient transfer function model that can accommodate the changing environment. A likelihood ratio statistic is used to test the stability of a traditional transfer function model. We investigate the performance of the test statistic in the finite sample case via simulation. Using some well‐known examples, we demonstrate clearly that the proposed functional‐coefficient model can substantially improve the accuracy of out‐of‐sample forecasts. In particular, our simple modification results in a 25% reduction in the mean squared errors of out‐of‐sample one‐step‐ahead forecasts for the gas‐furnace data of Box and Jenkins. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
105.
A simple, low cost interspike interval analyzer for the analysis of trains of nerve impulses is described. The analyzer is built with readily available integrated circuits and has been used to analyze spike trains in the lateral vestibular nucleus of cats. 相似文献
106.
Transmembrane ion channels play a crucial role in the existence of all living organisms. They partition the exterior from
the interior of the cell, maintain the proper ionic gradient across the cell membrane and facilitate signaling between cells.
To perform these functions, ion channels must be highly selective, allowing some types of ions to pass while blocking the
passage of others. Here we review a number of studies that have helped to elucidate the mechanisms by which ion channels discriminate
between ions of differing charge, focusing on four channel families as examples: gramicidin, ClC chloride, voltage-gated calcium
and potassium channels. The recent availability of high-resolution structural data has meant that the specific inter-atomic
interactions responsible for valence selectivity can be pinpointed. Not surprisingly, electrostatic considerations have been
shown to play an important role in ion specificity, although many details of the origins of this discrimination remain to
be determined.
Received 4 September 2005; received after revision 17 October 2005; accepted 2 November 2005 相似文献
107.
Amyloid β-induced FOXRED2 mediates neuronal cell death via inhibition of proteasome activity 总被引:1,自引:1,他引:0
Proteasome inhibition has been regarded as one of the mediators of Aβ neurotoxicity. In this study, we found that FOXRED2,
a novel endoplasmic reticulum (ER) residential protein, is highly up-regulated by Aβ in rat cortical neurons and SH-SY5Y cells.
Over-expression of FOXRED2 inhibits proteasome activity in the microsomal fractions containing ER and interferes with proteasome
assembly, as evidenced by gel filtration and native gel electrophoresis analysis. In contrast, reduced expression of FOXRED2
rescues Aβ-induced inhibition of proteasome activity. FOXRED2 is an unstable protein with two degradation boxes and one KEN
box, and its N-terminal oxidoreductase domain is required for proteasome inhibition. Ectopic expression of FOXRED2 induces
ER stress-mediated cell death via caspase-12, which is inhibited by Salubrinal. Further, down-regulation of FOXRED2 expression
attenuates Aβ-induced cell death and the ER stress response. These results suggest that up-regulated FOXRED2 inhibits proteasome
activity by interfering with 26S proteasome assembly to contribute to Aβ neurotoxicity via an ER stress response. 相似文献
108.
The endophenotype concept was initially proposed to enhance the power of genetic studies of complex disorders. It is closely related to the genetic component in a liability-threshold model; a perfect endophenotype should have a correlation of 1 with the genetic component of the liability to disease. In reality, a putative endophenotype is unlikely to be a perfect representation of the genetic component of disease liability. The magnitude of the correlation between a putative endophenotype and the genetic co... 相似文献
109.
Albagha OM Wani SE Visconti MR Alonso N Goodman K Brandi ML Cundy T Chung PY Dargie R Devogelaer JP Falchetti A Fraser WD Gennari L Gianfrancesco F Hooper MJ Van Hul W Isaia G Nicholson GC Nuti R Papapoulos S Montes Jdel P Ratajczak T Rea SL Rendina D Gonzalez-Sarmiento R Di Stefano M Ward LC Walsh JP Ralston SH;Genetic Determinants of Paget's Disease 《Nature genetics》2011,43(7):685-689
Paget's disease of bone (PDB) is a common disorder characterized by focal abnormalities of bone remodeling. We previously identified variants at the CSF1, OPTN and TNFRSF11A loci as risk factors for PDB by genome-wide association study. Here we extended this study, identified three new loci and confirmed their association with PDB in 2,215 affected individuals (cases) and 4,370 controls from seven independent populations. The new associations were with rs5742915 within PML on 15q24 (odds ratio (OR) = 1.34, P = 1.6 × 10(-14)), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10(-11)) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10(-10)). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10(-17)) with PDB. These seven loci explained ~13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB. 相似文献
110.