全文获取类型
收费全文 | 866篇 |
免费 | 62篇 |
出版年
2023年 | 7篇 |
2022年 | 18篇 |
2021年 | 36篇 |
2020年 | 18篇 |
2019年 | 17篇 |
2018年 | 23篇 |
2017年 | 26篇 |
2016年 | 44篇 |
2015年 | 85篇 |
2014年 | 66篇 |
2013年 | 52篇 |
2012年 | 79篇 |
2011年 | 94篇 |
2010年 | 56篇 |
2009年 | 36篇 |
2008年 | 55篇 |
2007年 | 55篇 |
2006年 | 31篇 |
2005年 | 36篇 |
2004年 | 28篇 |
2003年 | 22篇 |
2002年 | 16篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 1篇 |
1996年 | 3篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1978年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有928条查询结果,搜索用时 15 毫秒
861.
Adam Li Amber Mueller Brad English Anthony Arena Daniel Vera Alice E. Kane David A. Sinclair 《PLoS computational biology》2022,18(8)
Epigenetic clocks allow us to accurately predict the age and future health of individuals based on the methylation status of specific CpG sites in the genome and are a powerful tool to measure the effectiveness of longevity interventions. There is a growing need for methods to efficiently construct epigenetic clocks. The most common approach is to create clocks using elastic net regression modelling of all measured CpG sites, without first identifying specific features or CpGs of interest. The addition of feature selection approaches provides the opportunity to optimise the identification of predictive CpG sites. Here, we apply novel feature selection methods and combinatorial approaches including newly adapted neural networks, genetic algorithms, and ‘chained’ combinations. Human whole blood methylation data of ~470,000 CpGs was used to develop clocks that predict age with R2 correlation scores of greater than 0.73, the most predictive of which uses 35 CpG sites for a R2 correlation score of 0.87. The five most frequent sites across all clocks were modelled to build a clock with a R2 correlation score of 0.83. These two clocks are validated on two external datasets where they maintain excellent predictive accuracy. When compared with three published epigenetic clocks (Hannum, Horvath, Weidner) also applied to these validation datasets, our clocks outperformed all three models. We identified gene regulatory regions associated with selected CpGs as possible targets for future aging studies. Thus, our feature selection algorithms build accurate, generalizable clocks with a low number of CpG sites, providing important tools for the field. 相似文献
862.
863.
Primates - Sociality is widespread among group-living primates and is beneficial in many ways. Sociality amongst female bonobos (Pan paniscus) has been proposed to have evolved as a female... 相似文献
864.
865.
Nitsan Goldstein Aaron D. McKnight Jamie R.E. Carty Myrtha Arnold J. Nicholas Betley Amber L. Alhadeff 《Cell metabolism》2021,33(3):676-687.e5
- Download : Download high-res image (180KB)
- Download : Download full-size image
866.
867.
868.
Bhargavi Jayaraman Amber M. Smith Jason D. Fernandes 《Critical reviews in biochemistry and molecular biology》2016,51(5):379-394
Viruses are obligate parasites that rely heavily on host cellular processes for replication. The small number of proteins typically encoded by a virus is faced with selection pressures that lead to the evolution of distinctive structural properties, allowing each protein to maintain its function under constraints such as small genome size, high mutation rate, and rapidly changing fitness conditions. One common strategy for this evolution is to utilize small building blocks to generate protein oligomers that assemble in multiple ways, thereby diversifying protein function and regulation. In this review, we discuss specific cases that illustrate how oligomerization is used to generate a single defined functional state, to modulate activity via different oligomeric states, or to generate multiple functional forms via different oligomeric states. 相似文献
869.
870.
Dhiraj Acharya Amber M. Paul John F. Anderson Faqing Huang Fengwei Bai 《PLoS neglected tropical diseases》2015,9(10)
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell-derived CHIKV (CHIKVmos) has slower replication than mammalian cell-derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic effects and reduced antiviral responses. In addition, infection in mice show that CHIKVmos produces a lower level of viremia and less severe footpad swelling when compared with CHIKVvero. Interestingly, CHIKVmos has impaired ability to bind to glycosaminoglycan (GAG) receptors on mammalian cells. However, sequencing analysis shows that this impairment is not due to a mutation in the CHIKV E2 gene, which encodes for the viral receptor binding protein. Moreover, CHIKVmos progenies can regain GAG receptor binding capability and can replicate similarly to CHIKVvero after a single passage in mammalian cells. Furthermore, CHIKVvero and CHIKVmos no longer differ in replication when N-glycosylation of viral proteins was inhibited by growing these viruses in the presence of tunicamycin. Collectively, these results suggest that N-glycosylation of viral proteins within mosquito cells can result in loss of GAG receptor binding capability of CHIKV and reduction of its infectivity in mammalian cells. 相似文献