全文获取类型
收费全文 | 424篇 |
免费 | 44篇 |
国内免费 | 46篇 |
专业分类
514篇 |
出版年
2024年 | 2篇 |
2023年 | 11篇 |
2022年 | 34篇 |
2021年 | 36篇 |
2020年 | 22篇 |
2019年 | 26篇 |
2018年 | 32篇 |
2017年 | 18篇 |
2016年 | 13篇 |
2015年 | 38篇 |
2014年 | 35篇 |
2013年 | 24篇 |
2012年 | 21篇 |
2011年 | 24篇 |
2010年 | 14篇 |
2009年 | 14篇 |
2008年 | 19篇 |
2007年 | 22篇 |
2006年 | 18篇 |
2005年 | 17篇 |
2004年 | 18篇 |
2003年 | 19篇 |
2002年 | 13篇 |
2001年 | 12篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有514条查询结果,搜索用时 15 毫秒
31.
32.
Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and postmenopausal MZ cotwins discordant for hormonal therapy 下载免费PDF全文
Eija K. Laakkonen Rabah Soliymani Sira Karvinen Jaakko Kaprio Urho M. Kujala Marc Baumann Sarianna Sipilä Vuokko Kovanen Maciej Lalowski 《Aging cell》2017,16(6):1276-1287
Female middle age is characterized by a decline in skeletal muscle mass and performance, predisposing women to sarcopenia, functional limitations, and metabolic dysfunction as they age. Menopausal loss of ovarian function leading to low circulating level of 17β‐estradiol has been suggested as a contributing factor to aging‐related muscle deterioration. However, the underlying molecular mechanisms remain largely unknown and thus far androgens have been considered as a major anabolic hormone for skeletal muscle. We utilized muscle samples from 24 pre‐ and postmenopausal women to establish proteome‐wide profiles, associated with the difference in age (30–34 years old vs. 54–62 years old), menopausal status (premenopausal vs. postmenopausal), and use of hormone replacement therapy (HRT; user vs. nonuser). None of the premenopausal women used hormonal medication while the postmenopausal women were monozygotic (MZ) cotwin pairs of whom the other sister was current HRT user or the other had never used HRT. Label‐free proteomic analyses resulted in the quantification of 797 muscle proteins of which 145 proteins were for the first time associated with female aging using proteomics. Furthermore, we identified 17β‐estradiol as a potential upstream regulator of the observed differences in muscle energy pathways. These findings pinpoint the underlying molecular mechanisms of the metabolic dysfunction accruing upon menopause, thus having implications for understanding the complex functional interactions between female reproductive hormones and health. 相似文献
33.
《Expert review of proteomics》2013,10(1):65-77
This review describes how intimately proteogenomics and system biology are imbricated. Quantitative cell-wide monitoring of cellular processes and the analysis of this information is the basis for systems biology. Establishing the most comprehensive protein-parts list is an essential prerequisite prior to analysis of the cell-wide dynamics of proteins, their post-translational modifications, their complex network interactions and interpretation of these data as a whole. High-quality genome annotation is, thus, a crucial basis. Proteogenomics consists of high-throughput identification and characterization of proteins by extra-large shotgun MS/MS approaches and the integration of these data with genomic data. Discovery of the remaining unannotated genes, defining translational start sites, listing signal peptide processing events and post-translational modifications, are tasks that can currently be carried out at a full-genomic scale as soon as the genomic sequence is available. Proteomics is increasingly being used at the primary stage of genome annotation and such an approach may become standard in the near future for genome projects. Advantageously, the same experimental proteomic datasets may be used to characterize the specific metabolic traits of the organism under study. Undoubtedly, comparative genomics will experience a renaissance taking into account this new dimension. Synthetic biology aimed at re-engineering living systems will also benefit from these significant progresses. 相似文献
34.
Background and Aims
Although monocotyledonous plants comprise one of the two major groups of angiosperms and include >65 000 species, comprehensive genome analysis has been focused mainly on the Poaceae (grass) family. Due to this bias, most of the conclusions that have been drawn for monocot genome evolution are based on grasses. It is not known whether these conclusions apply to many other monocots.Methods
To extend our understanding of genome evolution in the monocots, Asparagales genomic sequence data were acquired and the structural properties of asparagus and onion genomes were analysed. Specifically, several available onion and asparagus bacterial artificial chromosomes (BACs) with contig sizes >35 kb were annotated and analysed, with a particular focus on the characterization of long terminal repeat (LTR) retrotransposons.Key Results
The results reveal that LTR retrotransposons are the major components of the onion and garden asparagus genomes. These elements are mostly intact (i.e. with two LTRs), have mainly inserted within the past 6 million years and are piled up into nested structures. Analysis of shotgun genomic sequence data and the observation of two copies for some transposable elements (TEs) in annotated BACs indicates that some families have become particularly abundant, as high as 4–5 % (asparagus) or 3–4 % (onion) of the genome for the most abundant families, as also seen in large grass genomes such as wheat and maize.Conclusions
Although previous annotations of contiguous genomic sequences have suggested that LTR retrotransposons were highly fragmented in these two Asparagales genomes, the results presented here show that this was largely due to the methodology used. In contrast, this current work indicates an ensemble of genomic features similar to those observed in the Poaceae. 相似文献35.
Background Rhizoctonia solani is a pathogenic fungus that causes serious diseases in many crops, including rice, wheat, and soybeans. In crop production, it is very important to understand the pathogenicity of this fungus, which is still elusive. It might be helpful to comprehensively understand its genomic information using different genome annotation strategies.MethodsAiming to improve the genome annotation of R. solani, we performed a proteogenomic study based on the existing data. Based on our study, a total of 1060 newly identified genes, 36 revised genes, 139 single amino acid variants (SAAVs), 8 alternative splicing genes, and diverse post-translational modifications (PTMs) events were identified in R. solani AG3. Further functional annotation on these 1060 newly identified genes was performed through homology analysis with its 5 closest relative fungi.ResultsBased on this, 2 novel candidate pathogenic genes, which might be associated with pathogen-host interaction, were discovered. In addition, in order to increase the reliability and novelty of the newly identified genes in R. solani AG3, 1060 newly identified genes were compared with the newly published available R. solani genome sequences of AG1, AG2, AG4, AG5, AG6, and AG8. There are 490 homologous sequences. We combined the proteogenomic results with the genome alignment results and finally identified 570 novel genes in R. solani.ConclusionThese findings extended R. solani genome annotation and provided a wealth of resources for research on R. solani. 相似文献
36.
37.
38.
Kristensen DM Chen BY Fofanov VY Ward RM Lisewski AM Kimmel M Kavraki LE Lichtarge O 《Protein science : a publication of the Protein Society》2006,15(6):1530-1536
The annotation of protein function has not kept pace with the exponential growth of raw sequence and structure data. An emerging solution to this problem is to identify 3D motifs or templates in protein structures that are necessary and sufficient determinants of function. Here, we demonstrate the recurrent use of evolutionary trace information to construct such 3D templates for enzymes, search for them in other structures, and distinguish true from spurious matches. Serine protease templates built from evolutionarily important residues distinguish between proteases and other proteins nearly as well as the classic Ser-His-Asp catalytic triad. In 53 enzymes spanning 33 distinct functions, an automated pipeline identifies functionally related proteins with an average positive predictive power of 62%, including correct matches to proteins with the same function but with low sequence identity (the average identity for some templates is only 17%). Although these template building, searching, and match classification strategies are not yet optimized, their sequential implementation demonstrates a functional annotation pipeline which does not require experimental information, but only local molecular mimicry among a small number of evolutionarily important residues. 相似文献
39.
完整的线粒体基因组已被广泛应用于分子进化、基因组学、系统发育等方面的研究。蚜虫是一类重要的农林业害虫, 但目前公开报道的蚜虫完整线粒体基因组非常有限, 因此获得更多的基因组数据对相关研究具有重要价值。本文报道了榕毛管蚜(Greenidea ficicola)、橘二叉蚜(Aphis aurantia)和油杉纩蚜(Mindarus keteleerifoliae) 3种蚜虫的完整线粒体基因组的序列、详细注释信息、基因结构图、密码子使用情况等。该数据集可为昆虫系统发育关系、种群分化格局、害虫防治等方面的工作提供帮助。 相似文献
40.
Immunoinformatics is an emerging new field that benefits from computational analyses and tools that facilitate the understanding of the immune system. A large number of immunoinformatics resources such as immune-related databases and analysis software are available through the World Wide Web for the benefit of the research community. However, immunoinformatics developments have sometimes remained isolated from mainstream bioinformatics. Therefore, there is clearly a need for integration, which will empower the exchange of data and annotations within the scientific community in a quick and efficient fashion. Here, we have chosen the Distributed Annotation System (DAS), for integrating in house annotations on experimental and predicted HLA I-restriction elements of CD8 T-cell epitopes with sequence and structural information. 相似文献