全文获取类型
收费全文 | 8642篇 |
免费 | 731篇 |
国内免费 | 1篇 |
专业分类
9374篇 |
出版年
2023年 | 40篇 |
2022年 | 91篇 |
2021年 | 184篇 |
2020年 | 79篇 |
2019年 | 121篇 |
2018年 | 143篇 |
2017年 | 119篇 |
2016年 | 260篇 |
2015年 | 410篇 |
2014年 | 477篇 |
2013年 | 559篇 |
2012年 | 732篇 |
2011年 | 701篇 |
2010年 | 499篇 |
2009年 | 460篇 |
2008年 | 588篇 |
2007年 | 580篇 |
2006年 | 520篇 |
2005年 | 496篇 |
2004年 | 478篇 |
2003年 | 454篇 |
2002年 | 410篇 |
2001年 | 76篇 |
2000年 | 55篇 |
1999年 | 73篇 |
1998年 | 93篇 |
1997年 | 74篇 |
1996年 | 62篇 |
1995年 | 47篇 |
1994年 | 57篇 |
1993年 | 60篇 |
1992年 | 37篇 |
1991年 | 43篇 |
1990年 | 27篇 |
1989年 | 26篇 |
1988年 | 32篇 |
1987年 | 21篇 |
1986年 | 22篇 |
1985年 | 13篇 |
1984年 | 14篇 |
1983年 | 23篇 |
1982年 | 11篇 |
1981年 | 18篇 |
1980年 | 12篇 |
1978年 | 13篇 |
1977年 | 13篇 |
1976年 | 7篇 |
1975年 | 7篇 |
1974年 | 8篇 |
1972年 | 5篇 |
排序方式: 共有9374条查询结果,搜索用时 0 毫秒
101.
An obligate intermediate along the slow folding pathway of a group II intron ribozyme 总被引:4,自引:1,他引:4
Most RNA molecules collapse rapidly and reach the native state through a pathway that contains numerous traps and unproductive intermediates. The D135 group II intron ribozyme is unusual in that it can fold slowly and directly to the native state, despite its large size and structural complexity. Here we use hydroxyl radical footprinting and native gel analysis to monitor the timescale of tertiary structure collapse and to detect the presence of obligate intermediates along the folding pathway of D135. We find that structural collapse and native folding of Domain 1 precede assembly of the entire ribozyme, indicating that D1 contains an on-pathway intermediate to folding of the D135 ribozyme. Subsequent docking of Domains 3 and 5, for which D1 provides a preorganized scaffold, appears to be very fast and independent of one another. In contrast to other RNAs, the D135 ribozyme undergoes slow tertiary collapse to a compacted state, with a rate constant that is also limited by the formation D1. These findings provide a new paradigm for RNA folding and they underscore the diversity of RNA biophysical behaviors. 相似文献
102.
103.
Vaulot D Lepère C Toulza E De la Iglesia R Poulain J Gaboyer F Moreau H Vandepoele K Ulloa O Gavory F Piganeau G 《PloS one》2012,7(6):e39648
Among small photosynthetic eukaryotes that play a key role in oceanic food webs, picoplanktonic Mamiellophyceae such as Bathycoccus, Micromonas, and Ostreococcus are particularly important in coastal regions. By using a combination of cell sorting by flow cytometry, whole genome amplification (WGA), and 454 pyrosequencing, we obtained metagenomic data for two natural picophytoplankton populations from the coastal upwelling waters off central Chile. About 60% of the reads of each sample could be mapped to the genome of Bathycoccus strain from the Mediterranean Sea (RCC1105), representing a total of 9 Mbp (sample T142) and 13 Mbp (sample T149) of non-redundant Bathycoccus genome sequences. WGA did not amplify all regions uniformly, resulting in unequal coverage along a given chromosome and between chromosomes. The identity at the DNA level between the metagenomes and the cultured genome was very high (96.3% identical bases for the three larger chromosomes over a 360 kbp alignment). At least two to three different genotypes seemed to be present in each natural sample based on read mapping to Bathycoccus RCC1105 genome. 相似文献
104.
Julie A. Woods John A. Hadfield Alan T. McGown Brian W. Fox 《Bioorganic & medicinal chemistry》1993,1(5)
Bis(2-bromo-4,5-dimethoxyphenyl)sulfide (5) and bis(2-bromo-4,5-dimethoxyphenyl) selenide (7) have been shown to block cells in the G2/M phase of the cell cycle, whereas the debromo (4, 6) equivalents do not. The dibromoselenide (7) is cytotoxic to tumour cells in vitro and has been shown to increase the mitotic index of treated cells. These biological effects are consistent with disruption of the mitotic apparatus. This agent does not inhibit microtubule assembly in vitro, but does bind to tubulin. Molecular modelling of these structures indicates that their spatial and electronic structures may make an important contribution to the biological activity. 相似文献
105.
Jacklyn N. Hellwege Nicholette D. Palmer W. Mark Brown Julie T. Ziegler S. Sandy An Xiuqing Guo Y.-D. Ida Chen Kent Taylor Gregory A. Hawkins Maggie C. Y. Ng Elizabeth K. Speliotes Carlos Lorenzo Jill M. Norris Jerome I. Rotter Lynne E. Wagenknecht Carl D. Langefeld Donald W. Bowden 《Human genetics》2015,134(2):215-215
106.
Joanne Blanchfield Julie Dutton Ron Hogg David Craik David Adams Richard Lewis Paul Alewood Istvan Toth 《Letters in Peptide Science》2001,8(3-5):235-239
The -conotoxin MII is a 16 amino acid long peptide toxinisolated from the marine snail, Conus magus. This toxinhas been found to be a highly selective and potent inhibitorof neuronal nicotinic acetylcholine receptors of the subtype32. To improve the bioavailability of this peptide, we havecoupled to the N-terminus of conotoxin MII, 2-amino-D,L-dodecanoic acid (Laa) creating a lipidic linear peptide whichwas then successfully oxidised to produce the correctly foldedconotoxin MII construct. 相似文献
107.
A primary assembly of a bovine haplotype block map based on a 15,036-single-nucleotide polymorphism panel genotyped in holstein-friesian cattle 下载免费PDF全文
Khatkar MS Zenger KR Hobbs M Hawken RJ Cavanagh JA Barris W McClintock AE McClintock S Thomson PC Tier B Nicholas FW Raadsma HW 《Genetics》2007,176(2):763-772
Analysis of data on 1000 Holstein-Friesian bulls genotyped for 15,036 single-nucleotide polymorphisms (SNPs) has enabled genomewide identification of haplotype blocks and tag SNPs. A final subset of 9195 SNPs in Hardy-Weinberg equilibrium and mapped on autosomes on the bovine sequence assembly (release Btau 3.1) was used in this study. The average intermarker spacing was 251.8 kb. The average minor allele frequency (MAF) was 0.29 (0.05-0.5). Following recent precedents in human HapMap studies, a haplotype block was defined where 95% of combinations of SNPs within a region are in very high linkage disequilibrium. A total of 727 haplotype blocks consisting of > or =3 SNPs were identified. The average block length was 69.7 +/- 7.7 kb, which is approximately 5-10 times larger than in humans. These blocks comprised a total of 2964 SNPs and covered 50,638 kb of the sequence map, which constitutes 2.18% of the length of all autosomes. A set of tag SNPs, which will be useful for further fine-mapping studies, has been identified. Overall, the results suggest that as many as 75,000-100,000 tag SNPs would be needed to track all important haplotype blocks in the bovine genome. This would require approximately 250,000 SNPs in the discovery phase. 相似文献
108.
Herman Justin Park Brian Awsare Bharat West Frances Crittendon Denine Evans Lilah Harach Mary Karp Julie Peedin Alexis LaNoue Marianna Goldsmith Barbara Warnick Eugene Baram Michael 《BMC anesthesiology》2019,19(1):1-6
Hypoxic preconditioning (HPC) may protect multiple organs from various injuries. We hypothesized that HPC would reduce lung injury in patients undergoing thoracoscopic lobectomy. In a prospective randomized controlled trial, 70 patients undergoing elective thoracoscopic lobectomy were randomly allocated to the HPC group or the control group. Three cycles of 5-min hypoxia and 3-min ventilation applied to the nondependent lung served as the HPC intervention. The primary outcome was the PaO2/FiO2 ratio. Secondary outcomes included postoperative pulmonary complications, pulmonary function, and duration of hospital stay. HPC significantly increased the PaO2/FiO2 ratio compared with the control at 30 min after one-lung ventilation and 7 days after operation. Compared with the control, it also significantly improved postoperative pulmonary function and markedly reduced the postoperative hospital stay duration. No significant differences between groups were observed in the incidence of pulmonary complications or overall postoperative morbidity. HPC improves postoperative oxygenation, enhances the recovery of pulmonary function, and reduces the duration of hospital stay in patients undergoing thoracoscopic lobectomy. This study was registered in the Chinese Clinical Trial Registry (ChiCTR-IPR-17011249) on April 27, 2017. 相似文献
109.
Julie Earl Daniel Rico Enrique Carrillo-de-Santa-Pau Benjamín Rodríguez-Santiago Marinela Méndez-Pertuz Herbert Auer Gonzalo Gómez Herbert Barton Grossman David G Pisano Wolfgang A Schulz Luis A Pérez-Jurado Alfredo Carrato Dan Theodorescu Stephen Chanock Alfonso Valencia Francisco X Real 《BMC genomics》2015,16(1)
Background
Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression.Results
Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events.Conclusions
Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1450-3) contains supplementary material, which is available to authorized users. 相似文献110.
Joanna F. Dipnall Julie A. Pasco Michael Berk Lana J. Williams Seetal Dodd Felice N. Jacka Denny Meyer 《PloS one》2016,11(2)