全文获取类型
收费全文 | 161篇 |
免费 | 25篇 |
出版年
2022年 | 1篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 8篇 |
2013年 | 6篇 |
2012年 | 11篇 |
2011年 | 10篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 7篇 |
2007年 | 8篇 |
2006年 | 10篇 |
2005年 | 4篇 |
2004年 | 6篇 |
2003年 | 8篇 |
2002年 | 6篇 |
2001年 | 10篇 |
2000年 | 9篇 |
1999年 | 13篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1986年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有186条查询结果,搜索用时 15 毫秒
11.
Mulder NJ Apweiler R Attwood TK Bairoch A Bateman A Binns D Biswas M Bradley P Bork P Bucher P Copley R Courcelle E Durbin R Falquet L Fleischmann W Gouzy J Griffith-Jones S Haft D Hermjakob H Hulo N Kahn D Kanapin A Krestyaninova M Lopez R Letunic I Orchard S Pagni M Peyruc D Ponting CP Servant F Sigrist CJ;InterPro Consortium 《Briefings in bioinformatics》2002,3(3):225-235
12.
Ponting CP 《Trends in genetics : TIG》2001,17(5):235-237
The initial analysis of the human genome draft sequence reveals that our 'book of life' is multi-authored. A small but significant proportion of our genes owes their heritage not to antecedent eukaryotes but instead to bacteria. The publicly funded Human Genome Project study indicates that about 0.5% of all human genes were copied into the genome from bacterial sources. Detailed sequence analyses point to these 'horizontal gene transfer' events having occurred relatively recently. So how did the human 'book of life' evolve to be a chimaera, part animal and part bacterium? And what was the probable evolutionary impact of such gene plagiarism? 相似文献
13.
The signalling pathway leading, for example, to actin cytoskeletal reorganisation, secretion or superoxide generation involves phospholipase D (PLD)-catalysed hydrolysis of phosphatidylcholine to generate phosphatidic acid, which appears to mediate the messenger functions of this pathway. Two PLD genes (PLD1 and PLD2) with similar domain structures have been doned and progress has been made in identifying the protein regulators of PLD1 activation, for example Arf and Rho family members. The activities of both PLD isoforms are dependent on phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and our sequence analysis suggested the presence of a pleckstrin homology (PH) domain in PLD1, although its absence has also been daimed. Investigation of the inositide dependence showed that a bis-phosphorylated lipid with a vicinal pair of phosphates was required for PLD1 activity. Furthermore, PLD1 bound specifically and with high affinity to lipid surfaces containing PI(4,5)P2 independently of the substrate phosphatidylcholine, suggesting a key role for the PH domain in PLD function. Importantly, a glutathione-S-transferase (GST) fusion protein comprising GST and the PH domain of PLD1 (GST-PLD1-PH) also bound specifically to supported lipid monolayers containing PI(4,5)P2. Point mutations within the PLD1 PH domain inhibited enzyme activity, whereas deletion of the domain both inhibited enzyme activity and disrupted normal PLD1 localisation. Thus, the functional PH domain regulates PLD by mediating its interaction with polyphosphoinositide-containing membranes; this might also induce a conformational change, thereby regulating catalytic activity. 相似文献
14.
15.
16.
Jayne Y. Hehir-Kwa Nienke Wieskamp Caleb Webber Rolph Pfundt Han G. Brunner Christian Gilissen Bert B. A. de Vries Chris P. Ponting Joris A. Veltman 《PLoS computational biology》2010,6(4)
Copy number variants (CNVs) have recently been recognized as a common form of genomic variation in humans. Hundreds of CNVs can be detected in any individual genome using genomic microarrays or whole genome sequencing technology, but their phenotypic consequences are still poorly understood. Rare CNVs have been reported as a frequent cause of neurological disorders such as mental retardation (MR), schizophrenia and autism, prompting widespread implementation of CNV screening in diagnostics. In previous studies we have shown that, in contrast to benign CNVs, MR-associated CNVs are significantly enriched in genes whose mouse orthologues, when disrupted, result in a nervous system phenotype. In this study we developed and validated a novel computational method for differentiating between benign and MR-associated CNVs using structural and functional genomic features to annotate each CNV. In total 13 genomic features were included in the final version of a Naïve Bayesian Tree classifier, with LINE density and mouse knock-out phenotypes contributing most to the classifier''s accuracy. After demonstrating that our method (called GECCO) perfectly classifies CNVs causing known MR-associated syndromes, we show that it achieves high accuracy (94%) and negative predictive value (99%) on a blinded test set of more than 1,200 CNVs from a large cohort of individuals with MR. These results indicate that this classification method will be of value for objectively prioritizing CNVs in clinical research and diagnostics. 相似文献
17.
18.
Coward K Ponting CP Zhang N Young C Huang CJ Chou CM Kashir J Fissore RA Parrington J 《Molecular reproduction and development》2011,78(1):48-56
Recent studies suggest that egg activation in mammals is triggered by a sperm-specific phospholipase C, PLCzeta. In other vertebrate species such as medaka fish, chickens, and quail, PLCzeta is also expressed as a testis-specific mRNA. Functional studies suggest that PLCzeta plays a similar role as a trigger of egg activation in these species. Here, we report the identification of PLCzeta orthologues in pufferfish species Takifugu rubripes (Fugu) and Tetraodon nigroviridis (Tetraodon). Unexpectedly in these species PLCzeta is expressed not in the testis, but in ovary and brain. Injection of pufferfish PLCzeta copy ribonucleic acid (cRNA) into mouse eggs failed to trigger calcium oscillations, unlike medaka PLCzeta cRNA. Our findings provide the first evidence that PLCzeta may be expressed in the egg, rather than the sperm, in some vertebrate species, and that its mechanism of action and physiologic role at fertilization may differ in different vertebrate species. 相似文献
19.
Michael B. Clark Paulo P. Amaral Felix J. Schlesinger Marcel E. Dinger Ryan J. Taft John L. Rinn Chris P. Ponting Peter F. Stadler Kevin V. Morris Antonin Morillon Joel S. Rozowsky Mark B. Gerstein Claes Wahlestedt Yoshihide Hayashizaki Piero Carninci Thomas R. Gingeras John S. Mattick 《PLoS biology》2011,9(7)
20.
Shinozuka H Hisano H Ponting RC Cogan NO Jones ES Forster JW Yamada T 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,112(1):167-177
The α-subunit of the casein protein kinase CK2 has been implicated in both light-regulated and circadian rhythm-controlled plant gene expression, including control of the flowering time. Two putative CK2α genes of perennial ryegrass (Lolium perenne L.) have been obtained from a cDNA library constructed with mRNA isolated from cold-acclimated crown tissue. The genomic organisation of the two genes was determined by Southern hybridisation analysis. Primer designs to the Lpck2a-1 and Lpck2a-2 cDNA sequences permitted the amplification of genomic products containing large intron sequences. Amplicon sequence analysis detected single nucleotide polymorphisms (SNPs) within the p150/112 reference mapping population. Validated SNPs, within diagnostic restriction enzyme sites, were used to design cleaved amplified polymorphic sequence (CAPS) assays. The Lpck2a-1 CAPS marker was assigned to perennial ryegrass linkage group (LG) 4 and the Lpck2a-2 CAPS marker was assigned to LG2. The location of the Lpck2a-1 gene locus supports the previous conclusion of conserved synteny between perennial ryegrass LG4, the Triticeae homoeologous group 5L chromosomes and the corresponding segment of rice chromosome 3. Allelic variation at the Lpck2a-1 and Lpck2a-2 gene loci was correlated with phenotypic variation for heading date and winter survival, respectively. SNP polymorphism may be used for the further study of the role of CK2α genes in the initiation of reproductive development and winter hardiness in grasses. 相似文献