全文获取类型
收费全文 | 1452篇 |
免费 | 83篇 |
国内免费 | 2篇 |
专业分类
1537篇 |
出版年
2023年 | 2篇 |
2022年 | 25篇 |
2021年 | 21篇 |
2020年 | 11篇 |
2019年 | 23篇 |
2018年 | 20篇 |
2017年 | 20篇 |
2016年 | 35篇 |
2015年 | 87篇 |
2014年 | 66篇 |
2013年 | 82篇 |
2012年 | 144篇 |
2011年 | 119篇 |
2010年 | 78篇 |
2009年 | 66篇 |
2008年 | 90篇 |
2007年 | 93篇 |
2006年 | 97篇 |
2005年 | 99篇 |
2004年 | 83篇 |
2003年 | 60篇 |
2002年 | 62篇 |
2001年 | 17篇 |
2000年 | 16篇 |
1999年 | 6篇 |
1998年 | 19篇 |
1997年 | 9篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 14篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 8篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1983年 | 6篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 5篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1966年 | 1篇 |
1965年 | 2篇 |
1964年 | 1篇 |
1929年 | 1篇 |
排序方式: 共有1537条查询结果,搜索用时 15 毫秒
101.
At early stages of biochemical evolution, the complexity of replicating molecules was limited by unavoidably high mutation rates. In an RNA world, prior to the appearance of cellular life, an increase in molecular length, and thus in functional complexity, could have been mediated by modular evolution. We describe here a scenario in which short, replicating RNA sequences are selected to perform a simple function. Molecular function is represented through the secondary structure corresponding to each sequence, and a given target secondary structure yields the optimal function in the environment where the population evolves. The combination of independently evolved populations may have facilitated the emergence of larger molecules able to perform more complex functions (including RNA replication) that could arise as a combination of simpler ones. We quantitatively show that modular evolution has relevant advantages with respect to the direct evolution of large functional molecules, among them the allowance of higher mutation rates, the shortening of evolutionary times, and the very possibility of finding complex structures that could not be otherwise directly selected. 相似文献
102.
103.
Gorodkin J Cirera S Hedegaard J Gilchrist MJ Panitz F Jørgensen C Scheibye-Knudsen K Arvin T Lumholdt S Sawera M Green T Nielsen BJ Havgaard JH Rosenkilde C Wang J Li H Li R Liu B Hu S Dong W Li W Yu J Wang J Staefeldt HH Wernersson R Madsen LB Thomsen B Hornshøj H Bujie Z Wang X Wang X Bolund L Brunak S Yang H Bendixen C Fredholm M 《Genome biology》2007,8(4):R45-16
104.
Ágnes Baross Allen D Delaney H Irene Li Tarun Nayar Stephane Flibotte Hong Qian Susanna Y Chan Jennifer Asano Adrian Ally Manqiu Cao Patricia Birch Mabel Brown-John Nicole Fernandes Anne Go Giulia Kennedy Sylvie Langlois Patrice Eydoux JM Friedman Marco A Marra 《BMC bioinformatics》2007,8(1):1-18
Background
Genomic deletions and duplications are important in the pathogenesis of diseases, such as cancer and mental retardation, and have recently been shown to occur frequently in unaffected individuals as polymorphisms. Affymetrix GeneChip whole genome sampling analysis (WGSA) combined with 100 K single nucleotide polymorphism (SNP) genotyping arrays is one of several microarray-based approaches that are now being used to detect such structural genomic changes. The popularity of this technology and its associated open source data format have resulted in the development of an increasing number of software packages for the analysis of copy number changes using these SNP arrays.Results
We evaluated four publicly available software packages for high throughput copy number analysis using synthetic and empirical 100 K SNP array data sets, the latter obtained from 107 mental retardation (MR) patients and their unaffected parents and siblings. We evaluated the software with regards to overall suitability for high-throughput 100 K SNP array data analysis, as well as effectiveness of normalization, scaling with various reference sets and feature extraction, as well as true and false positive rates of genomic copy number variant (CNV) detection.Conclusion
We observed considerable variation among the numbers and types of candidate CNVs detected by different analysis approaches, and found that multiple programs were needed to find all real aberrations in our test set. The frequency of false positive deletions was substantial, but could be greatly reduced by using the SNP genotype information to confirm loss of heterozygosity. 相似文献105.
Svea Dittmann Annika Schmid Susanna Richter Konrad Trülzsch Jürgen Heesemann Gottfried Wilharm 《BMC microbiology》2007,7(1):67
Background
Pathogenic yersiniae (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica) share a virulence plasmid encoding a type three secretion system (T3SS). This T3SS comprises more than 40 constituents. Among these are the transport substrates called Yops (Yersinia outer proteins), the specific Yop chaperones (Sycs), and the Ysc (Yop secretion) proteins which form the transport machinery. The effectors YopO and YopP are encoded on an operon together with SycO, the chaperone of YopO. The characterization of SycO is the focus of this study. 相似文献106.
Bonora GM Drioli S Ballico M Faccini A Corradini R Cogoi S Xodo L 《Nucleosides, nucleotides & nucleic acids》2007,26(6-7):661-664
The conjugation of a bioactive, fluorescent PNA sequence to high-molecular weight poly(ethylene glycol) (PEG) is described and the properties of the PEG-PNA conjugate are evaluated. 相似文献
107.
108.
109.
110.
Vacca F D'Ambrosi N Nestola V Amadio S Giustizieri M Cucchiaroni ML Tozzi A Velluz MC Mercuri NB Volonté C 《Glycobiology》2011,21(5):634-643
N-Glycosylation affects the function of ion channels at the level of multisubunit assembly, protein trafficking, ligand binding and channel opening. Like the majority of membrane proteins, ionotropic P2X receptors for extracellular ATP are glycosylated in their extracellular moiety. Here, we used site-directed mutagenesis to the four predicted N-glycosylation sites of P2X(3) receptor (Asn(139), Asn(170), Asn(194) and Asn(290)) and performed comparative analysis of the role of N-glycans on protein stability, plasma membrane delivery, trimer formation and inward currents. We have found that in transiently transfected HEK293 cells, Asn(170) is apparently the most important site for receptor stability, since its mutation causes a primary loss in protein content and indirect failure in membrane expression, oligomeric association and inward current responses. Even stronger effects are obtained when mutating Thr(172) in the same glycosylation consensus. Asn(194) and Asn(290) are the most dispensable, since even their simultaneous mutation does not affect any tested receptor feature. All double mutants containing Asn(170) mutation or the Asn(139)/Asn(290) double mutant are instead almost unable to assemble into a functional trimeric structure. The main emerging finding is that the inability to assemble into trimers might account for the impaired function in P2X(3) mutants where residue Asn(170) is replaced. These results improve our knowledge about the role of N-glycosylation in proper folding and oligomeric association of P2X(3) receptor. 相似文献