全文获取类型
收费全文 | 1179篇 |
免费 | 89篇 |
国内免费 | 4篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 25篇 |
2020年 | 22篇 |
2019年 | 19篇 |
2018年 | 26篇 |
2017年 | 21篇 |
2016年 | 38篇 |
2015年 | 55篇 |
2014年 | 65篇 |
2013年 | 93篇 |
2012年 | 103篇 |
2011年 | 80篇 |
2010年 | 46篇 |
2009年 | 59篇 |
2008年 | 57篇 |
2007年 | 59篇 |
2006年 | 56篇 |
2005年 | 55篇 |
2004年 | 52篇 |
2003年 | 59篇 |
2002年 | 56篇 |
2001年 | 6篇 |
2000年 | 12篇 |
1999年 | 11篇 |
1998年 | 15篇 |
1997年 | 15篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 13篇 |
1991年 | 11篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 13篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1981年 | 8篇 |
1980年 | 4篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1971年 | 2篇 |
1967年 | 4篇 |
1966年 | 3篇 |
1955年 | 2篇 |
排序方式: 共有1272条查询结果,搜索用时 15 毫秒
91.
Chandree?L. Beaulieu Jacek Majewski Jeremy Schwartzentruber Mark?E. Samuels Bridget?A. Fernandez Francois?P. Bernier Michael Brudno Bartha Knoppers Janet Marcadier David Dyment Shelin Adam Dennis?E. Bulman Steve?J.M. Jones Denise Avard Minh?Thu Nguyen Francois Rousseau Christian Marshall Richard?F. Wintle Yaoqing Shen Stephen?W. Scherer FORGE Canada Consortium Jan?M. Friedman Jacques?L. Michaud Kym?M. Boycott 《American journal of human genetics》2014,94(6):809-817
Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE’s impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally. 相似文献
92.
93.
Kazuyuki Tanabe Toshihiro Mita Thibaut Jombart Anders Eriksson Shun Horibe Nirianne Palacpac Lisa Ranford-Cartwright Hiromi Sawai Naoko Sakihama Hiroshi Ohmae Masatoshi Nakamura Marcelo U. Ferreira Ananias A. Escalante Franck Prugnolle Anders Björkman Anna Färnert Akira Kaneko Toshihiro Horii Andrea Manica Hirohisa Kishino Francois Balloux 《Current biology : CB》2010,20(14):1283-1289
94.
95.
? Premise of the study: New primers were developed for the nuclear marker glutamine synthetase (ncpGS) in Oxalidaceae. ? Methods and Results: New forward and reverse primers were designed and tested across a wide range of Oxalidaceae. Selected taxa were sequenced to confirm homology. Potential for phylogenetic study was assessed by comparing sequenced taxa with commonly used nuclear and plastid markers. ? Conclusions: Four out of five Oxalidaceae genera and all tested Oxalis spp. amplified successfully. Sequencing confirmed homology of the amplicon. Parsimony analysis of ncpGS showed that it is a promising candidate for future phylogenetic work in Oxalidaceae. 相似文献
96.
97.
Background
Both bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) infections are currently wide-spread in the Swedish dairy cattle population. Surveys of antibody levels in bulk tank milk have shown very high nationwide prevalences of both BCV and BRSV, with large variations between regions. In the Swedish beef cattle population however, no investigations have yet been performed regarding the prevalence and geographical distribution of BCV and BRSV. A cross-sectional serological survey for BCV and BRSV was carried out in Swedish beef cattle to explore any geographical patterns of these infections. 相似文献98.
Donald M Gardiner Kemal Kazan Sebastien Praud Francois J Torney Anca Rusu John M Manners 《BMC plant biology》2010,10(1):289
Background
The fungal pathogen Fusarium graminearum causes Fusarium Head Blight (FHB) disease on wheat which can lead to trichothecene mycotoxin (e.g. deoxynivalenol, DON) contamination of grain, harmful to mammalian health. DON is produced at low levels under standard culture conditions when compared to plant infection but specific polyamines (e.g. putrescine and agmatine) and amino acids (e.g. arginine and ornithine) are potent inducers of DON by F. graminearum in axenic culture. Currently, host factors that promote mycotoxin synthesis during FHB are unknown, but plant derived polyamines could contribute to DON induction in infected heads. However, the temporal and spatial accumulation of polyamines and amino acids in relation to that of DON has not been studied. 相似文献99.
Oanh N. L. Le Francis Rodier Francois Fontaine Jean‐Philippe Coppe Judith Campisi James DeGregori Caroline Laverdière Victor Kokta Elie Haddad Christian M. Beauséjour 《Aging cell》2010,9(3):398-409
Exposure to IR has been shown to induce the formation of senescence markers, a phenotype that coincides with lifelong delayed repair and regeneration of irradiated tissues. We hypothesized that IR‐induced senescence markers could persist long‐term in vivo, possibly contributing to the permanent reduction in tissue functionality. Here, we show that mouse tissues exposed to a sublethal dose of IR display persistent (up to 45 weeks, the maximum time analyzed) DNA damage foci and increased p16INK4a expression, two hallmarks of cellular senescence and aging. BrdU‐labeling experiments revealed that IR‐induced damaged cells are preferentially eliminated, at least partially, in a tissue‐dependent manner. Unexpectedly, the accumulation of damaged cells was found to occur independent from the DNA damage response modulator p53, and from an intact immune system, as their levels were similar in wild‐type and Rag2?/? γC?/? mice, the latter being deficient in T, B, and NK cells. Together, our results provide compelling evidence that exposure to IR induces long‐term expression of senescence markers in vivo, an effect that may contribute to the reduced tissue functionality observed in cancer survivors. 相似文献
100.
Jirasko V Montserret R Lee JY Gouttenoire J Moradpour D Penin F Bartenschlager R 《PLoS pathogens》2010,6(12):e1001233
Non-structural protein 2 (NS2) plays an important role in hepatitis C virus (HCV) assembly, but neither the exact contribution of this protein to the assembly process nor its complete structure are known. In this study we used a combination of genetic, biochemical and structural methods to decipher the role of NS2 in infectious virus particle formation. A large panel of NS2 mutations targeting the N-terminal membrane binding region was generated. They were selected based on a membrane topology model that we established by determining the NMR structures of N-terminal NS2 transmembrane segments. Mutants affected in virion assembly, but not RNA replication, were selected for pseudoreversion in cell culture. Rescue mutations restoring virus assembly to various degrees emerged in E2, p7, NS3 and NS2 itself arguing for an interaction between these proteins. To confirm this assumption we developed a fully functional JFH1 genome expressing an N-terminally tagged NS2 demonstrating efficient pull-down of NS2 with p7, E2 and NS3 and, to a lower extent, NS5A. Several of the mutations blocking virus assembly disrupted some of these interactions that were restored to various degrees by those pseudoreversions that also restored assembly. Immunofluorescence analyses revealed a time-dependent NS2 colocalization with E2 at sites close to lipid droplets (LDs) together with NS3 and NS5A. Importantly, NS2 of a mutant defective in assembly abrogates NS2 colocalization around LDs with E2 and NS3, which is restored by a pseudoreversion in p7, whereas NS5A is recruited to LDs in an NS2-independent manner. In conclusion, our results suggest that NS2 orchestrates HCV particle formation by participation in multiple protein-protein interactions required for their recruitment to assembly sites in close proximity of LDs. 相似文献