全文获取类型
收费全文 | 343篇 |
免费 | 26篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 13篇 |
2018年 | 9篇 |
2017年 | 9篇 |
2016年 | 9篇 |
2015年 | 17篇 |
2014年 | 30篇 |
2013年 | 30篇 |
2012年 | 33篇 |
2011年 | 16篇 |
2010年 | 12篇 |
2009年 | 17篇 |
2008年 | 16篇 |
2007年 | 18篇 |
2006年 | 16篇 |
2005年 | 9篇 |
2004年 | 7篇 |
2003年 | 6篇 |
2002年 | 2篇 |
2001年 | 11篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 13篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1976年 | 2篇 |
1971年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有369条查询结果,搜索用时 31 毫秒
31.
Background
Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction. 相似文献32.
Cullin 4 (Cul4), a member of the evolutionally conserved cullin protein family, serves as a scaffold to assemble multisubunit ubiquitin E3 ligase complexes. Cul4 interacts with the Ring finger-containing protein ROC1 through its C-terminal cullin domain and with substrate recruiting subunit(s) through its N-terminus. Previous studies have demonstrated that Cul4 E3 ligase ubiquitylates key regulators in cell cycle control and mediates their degradation through the proteasomal pathway, thus contributing to genome stability. Recent studies from several groups have revealed that Cul4 E3 ligase can target histones for ubiquitylation, and importantly, ubiquitylation of histones may facilitate the cellular response to DNA damage. Therefore, histone ubiquitylation by Cul4 E3 ligase constitutes a novel mechanism through which Cul4 regulates chromatin function and maintains genomic integrity. We outline these studies and suggest that histone ubiquitylation might play important roles in Cul4-regualted chromatin function including the cellular response to DNA damage and heterochromatin gene silencing. 相似文献
33.
Yvet E Noordman Patrick AM Jansen Wiljan JAJ Hendriks 《Journal of molecular signaling》2006,1(1):1-11
Background
Spatio-temporal control of extracellular signal-regulated kinase (ERK) activity, a critical determinant of the cell's response to growth factors, requires timely dephosphorylation of its regulatory tyrosine and/or threonine residue by MAPK phosphatases. We studied the physiological role of kinase interaction motif (KIM)-containing protein tyrosine phosphatases (PTPs) in the control of EGF- and NGF-induced ERK activity in neuroendocrine PC12 cells.Results
We found a single KIM-containing PTP to be endogenously expressed in rat PC12 cells: the transmembrane PTPRR isoform termed PCPTP1. Protein knock-down of PCPTP1, or fourfold overexpression of its mouse orthologue, PTPBR7, left EGF- and NGF-induced ERK1/2 activity in PC12 cells unaltered. Ectopic expression of cytosolic PTPRR isoforms, however, resulted in reduced EGF-induced ERK1/2 activity, an effect that was dependent on the phosphatase activity and the KIM-domain of these PTPs.Conclusion
The finding that robust changes in tyrosine-specific MAPK phosphatase expression levels have minor effects on temporal ERK1/2 activity control in PC12 cells suggests that dual-specificity MAPK phosphatases may act as major regulators of growth factor-induced ERK1/2 signaling in these cells. 相似文献34.
Albart Coster John WM Bastiaansen Mario PL Calus Johan AM van Arendonk Henk Bovenhuis 《遗传、选种与进化》2010,42(1):9
The objective of this simulation study was to compare the effect of the number of QTL and distribution of QTL variance on the accuracy of breeding values estimated with genomewide markers (MEBV). Three distinct methods were used to calculate MEBV: a Bayesian Method (BM), Least Angle Regression (LARS) and Partial Least Square Regression (PLSR). The accuracy of MEBV calculated with BM and LARS decreased when the number of simulated QTL increased. The accuracy decreased more when QTL had different variance values than when all QTL had an equal variance. The accuracy of MEBV calculated with PLSR was affected neither by the number of QTL nor by the distribution of QTL variance. Additional simulations and analyses showed that these conclusions were not affected by the number of individuals in the training population, by the number of markers and by the heritability of the trait. Results of this study show that the effect of the number of QTL and distribution of QTL variance on the accuracy of MEBV depends on the method that is used to calculate MEBV. 相似文献
35.
A series of 1-ns MD simulations were performed on the scorpion toxin Lqh III in native and disulfide bond broken states. The removal of disulfide bonds has caused hydrogen bond network alteration in the five-residue turn, the long loop, the alpha-helix, the loop connecting strands II and III, and the C-terminal region. In addition and more importantly, it has influenced the amplitude of the fluctuations of five-residue turn, loops, and C-terminal region with a minor effect on the fluctuations of the cysteines in the broken bond sites. These findings suggest that disulfide bonds are not the most important factors in rigidifying their own locations, while they have more important effects at a global scale. Furthermore, our results reveal that disulfide bonds have considerable influence on the functionally important essential modes of motions and the correlations between the motions of the binding site residues. Therefore, we can conclude that disulfide bonds have a crucial role in modulating the function via adjusting the dynamics of scorpion toxin molecules. Although this conclusion cannot be generalized to all peptides and proteins, it demonstrates the importance of more investigations on this aspect of disulfide bond efficacy. 相似文献
36.
Sugars are involved in many metabolic and signalling pathways in plants. Sugar signals may also contribute to immune responses against pathogens and probably function as priming molecules leading to pathogen-associated molecular patterns (PAMP)-triggered immunity and effector-triggered immunity in plants. These putative roles also depend greatly on coordinated relationships with hormones and the light status in an intricate network. Although evidence in favour of sugar-mediated plant immunity is accumulating, more in-depth fundamental research is required to unravel the sugar signalling pathways involved. This might pave the way for the use of biodegradable sugar-(like) compounds to counteract plant diseases as cheaper and safer alternatives for toxic agrochemicals. 相似文献
37.
38.
Ryanne JM Lemmens Annick AA Timmermans Yvonne JM Janssen-Potten Rob JEM Smeets Henk AM Seelen 《BMC neurology》2012,12(1):1-17
Background
Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy.Methods
A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics.Results
Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks.Conclusions
Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed. 相似文献39.
40.