全文获取类型
收费全文 | 121篇 |
免费 | 21篇 |
出版年
2018年 | 1篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 2篇 |
2013年 | 3篇 |
2012年 | 7篇 |
2011年 | 8篇 |
2010年 | 6篇 |
2009年 | 4篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 1篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 7篇 |
1974年 | 3篇 |
1973年 | 7篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有142条查询结果,搜索用时 62 毫秒
61.
62.
A chimeric gene consisting of DNA coding for the 15-amino acid signal peptide of influenza virus hemagglutinin and the C-terminal 694 amino acids of SV40 large T antigen was inserted into a bovine papilloma virus (BPV) expression vector and introduced into NIH-3T3 cells. Cell lines were obtained that express high levels (approximately 5 X 10(6) molecules/cell) of the chimeric protein (HA-T antigen). The biochemical properties and intracellular localization of HA-T antigens were compared with those of wild-type T antigen. Wild-type T antigen. Wild-type T antigen is located chiefly in the cell nucleus, although a small fraction is detected on the cell surface. By contrast, HA-T antigen is found exclusively in the endoplasmic reticulum (ER). During biosynthesis, HA-T antigen is co-translationally translocated across the membrane of the ER, the signal peptide is cleaved and a mannose-rich oligosaccharide is attached to the polypeptide (T antigen contains one potential N-linked glycosylation site at Asn154). HA-T antigen does not become terminally glycosylated or acylated and little or none reaches the cell surface. These results suggest that T antigen is incapable of being transported along the exocytotic pathway. To explain the presence of wild-type T antigen on the surface of SV40-transformed cells, an alternative route is proposed involving transport of T antigen from the nucleus to the cell surface. 相似文献
63.
64.
65.
C André Lévesque Henk Brouwer Liliana Cano John P Hamilton Carson Holt Edgar Huitema Sylvain Raffaele Gregg P Robideau Marco Thines Joe Win Marcelo M Zerillo Gordon W Beakes Jeffrey L Boore Dana Busam Bernard Dumas Steve Ferriera Susan I Fuerstenberg Claire MM Gachon Elodie Gaulin Francine Govers Laura Grenville-Briggs Neil Horner Jessica Hostetler Rays HY Jiang Justin Johnson Theerapong Krajaejun Haining Lin Harold JG Meijer Barry Moore Paul Morris Vipaporn Phuntmart Daniela Puiu Jyoti Shetty Jason E Stajich Sucheta Tripathy Stephan Wawra Pieter van West Brett R Whitty Pedro M Coutinho Bernard Henrissat Frank Martin Paul D Thomas Brett M Tyler Ronald P De Vries Sophien Kamoun Mark Yandell Ned Tisserat C Robin Buell 《Genome biology》2010,11(7):1-22
66.
Jennifer G Sambrook Arman Bashirova Hanne Andersen Mike Piatak George S Vernikos Penny Coggill Jeff D Lifson Mary Carrington Stephan Beck 《BMC genomics》2006,7(1):1-8
Background
The recent advancement in human genome sequencing and genotyping has revealed millions of single nucleotide polymorphisms (SNP) which determine the variation among human beings. One of the particular important projects is The International HapMap Project which provides the catalogue of human genetic variation for disease association studies. In this paper, we analyzed the genotype data in HapMap project by using National Institute of Environmental Health Sciences Environmental Genome Project (NIEHS EGP) SNPs. We first determine whether the HapMap data are transferable to the NIEHS data. Then, we study how well the HapMap SNPs capture the untyped SNPs in the region. Finally, we provide general guidelines for determining whether the SNPs chosen from HapMap may be able to capture most of the untyped SNPs.Results
Our analysis shows that HapMap data are not robust enough to capture the untyped variants for most of the human genes. The performance of SNPs for European and Asian samples are marginal in capturing the untyped variants, i.e. approximately 55%. Expectedly, the SNPs from HapMap YRI panel can only capture approximately 30% of the variants. Although the overall performance is low, however, the SNPs for some genes perform very well and are able to capture most of the variants along the gene. This is observed in the European and Asian panel, but not in African panel. Through observation, we concluded that in order to have a well covered SNPs reference panel, the SNPs density and the association among reference SNPs are important to estimate the robustness of the chosen SNPs.Conclusion
We have analyzed the coverage of HapMap SNPs using NIEHS EGP data. The results show that HapMap SNPs are transferable to the NIEHS SNPs. However, HapMap SNPs cannot capture some of the untyped SNPs and therefore resequencing may be needed to uncover more SNPs in the missing region. 相似文献67.
68.
Petra Leidinger Christina Backes Stephanie Deutscher Katja Schmitt Sabine C Mueller Karen Frese Jan Haas Klemens Ruprecht Friedemann Paul Cord St?hler Christoph JG Lang Benjamin Meder Tamas Bartfai Eckart Meese Andreas Keller 《Genome biology》2013,14(7):R78
Background
Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples.Results
We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies.Conclusions
The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases. 相似文献69.
Duncan EL Danoy P Kemp JP Leo PJ McCloskey E Nicholson GC Eastell R Prince RL Eisman JA Jones G Sambrook PN Reid IR Dennison EM Wark J Richards JB Uitterlinden AG Spector TD Esapa C Cox RD Brown SD Thakker RV Addison KA Bradbury LA Center JR Cooper C Cremin C Estrada K Felsenberg D Glüer CC Hadler J Henry MJ Hofman A Kotowicz MA Makovey J Nguyen SC Nguyen TV Pasco JA Pryce K Reid DM Rivadeneira F Roux C Stefansson K Styrkarsdottir U Thorleifsson G Tichawangana R Evans DM Brown MA 《PLoS genetics》2011,7(4):e1001372
Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. 相似文献
70.
Viktoria Gloy Wolfgang Langhans Jacquelien JG Hillebrand Nori Geary Lori Asarian 《Biology of sex differences》2011,2(1):1-13