全文获取类型
收费全文 | 350篇 |
免费 | 67篇 |
出版年
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 8篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 13篇 |
2015年 | 22篇 |
2014年 | 22篇 |
2013年 | 20篇 |
2012年 | 27篇 |
2011年 | 28篇 |
2010年 | 22篇 |
2009年 | 17篇 |
2008年 | 13篇 |
2007年 | 11篇 |
2006年 | 9篇 |
2005年 | 19篇 |
2004年 | 13篇 |
2003年 | 16篇 |
2002年 | 7篇 |
2001年 | 10篇 |
2000年 | 9篇 |
1999年 | 11篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 12篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1975年 | 2篇 |
1965年 | 1篇 |
1957年 | 1篇 |
1954年 | 1篇 |
1950年 | 1篇 |
1945年 | 1篇 |
1938年 | 1篇 |
1935年 | 1篇 |
1933年 | 1篇 |
1915年 | 1篇 |
1913年 | 1篇 |
排序方式: 共有417条查询结果,搜索用时 31 毫秒
41.
42.
Sawcer S Ban M Maranian M Yeo TW Compston A Kirby A Daly MJ De Jager PL Walsh E Lander ES Rioux JD Hafler DA Ivinson A Rimmler J Gregory SG Schmidt S Pericak-Vance MA Akesson E Hillert J Datta P Oturai A Ryder LP Harbo HF Spurkland A Myhr KM Laaksonen M Booth D Heard R Stewart G Lincoln R Barcellos LF Hauser SL Oksenberg JR Kenealy SJ Haines JL;International Multiple Sclerosis Genetics Consortium 《American journal of human genetics》2005,77(3):454-467
To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis. Multipoint nonparametric linkage analysis revealed highly significant linkage in the major histocompatibility complex (MHC) on chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18). This set of markers achieved a mean information extraction of 79.3% across the genome, with a Mendelian inconsistency rate of only 0.002%. Stratification based on carriage of the multiple sclerosis–associated DRB1*1501 allele failed to identify any other region of linkage with genomewide significance. However, ordered-subset analysis suggested that there may be an additional locus on chromosome 19p13 that acts independent of the main MHC locus. These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for multiple sclerosis will have to involve large sample sizes and an association-based methodology. 相似文献
43.
The chromatographic purification of biological macromolecules requires a novel approach to overcome some of the pore size limitations of commercially available resins. Membrane adsorbers offer the potential for better resolution as well as productivity. Sharp peaks are gained by the rapid exchange rate with the adsorbing membranes associated with the convective flow path, in contrast to the pore diffusion requirement for resin exchange. The resolution advantage is preserved even when the very short bed heights of membranes are exploited for the purpose of exceptionally high flow rates and productivity.Breakthrough experiments were used to assess the membrane dynamic loading capacities of flexible macromolecules using supercoiled (SC) DNA as a model system. In contrast to reports for smaller biomolecules such as proteins and antibodies, the dynamic capacity for DNA was found to be highly dependent on flow rates and concentrations. Increasing flow rates induced DNA elongation, which increased the surface coverage and, in turn, lowered the capacity. Increasing concentrations beyond C*, the overlap concentration, led to exclusion-volume interactions, which reduced the size of DNA and increased the membrane adsorber capacity. In the chromatographic mode, membranes with a strongly positive charge were able to resolve various isoforms of DNA, surpassing the capabilities of analogous chromatographic resins. In this study, we found that the convective-flow-induced-structural behavior of DNA is responsible for the resolution in separation. 相似文献
44.
SUMMARY The mainstream forestry policy in many European countries is to convert coniferous plantations into (semi-natural) deciduous woodlands. However, woodlands are the main habitat for Ixodes ricinus ticks. Therefore, assessing to what extent tick abundance and infection with Borrelia spirochetes are affected by forest composition and structure is a prerequisite for effective prevention of Lyme borreliosis. We selected a total of 25 pine and oak stands, both with and without an abundant shrub layer, in northern Belgium and estimated tick abundance between April and October 2008-2010. Additionally, the presence of deer beds was used as an indicator of relative deer habitat use. Borrelia infections in questing nymphs were determined by polymerase chain reactions. The abundance of larvae, nymphs, and adults was higher in oak stands compared to pine stands and increased with increasing shrub cover, most likely due to differences in habitat use by the ticks' main hosts. Whereas tick abundance was markedly higher in structure-rich oak stands compared to homogeneous pine stands, the Borrelia infection rates in nymphs did not differ significantly. Our results indicate that conversion towards structure-rich deciduous forests might create more suitable tick habitats, but we were unable to detect an effect on the infection rate. 相似文献
45.
Carter SL Cibulskis K Helman E McKenna A Shen H Zack T Laird PW Onofrio RC Winckler W Weir BA Beroukhim R Pellman D Levine DA Lander ES Meyerson M Getz G 《Nature biotechnology》2012,30(5):413-421
We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity. 相似文献
46.
Although there is no doubt that significant morbidity and mortality occur during annual influenza epidemics, the role of contextual circumstances, which catalyze seasonal influenza transmission, remains unclear. Weather conditions are believed to affect virus survival, efficiency of transmission and host immunity, but seasonality may also be driven by a tendency of people to congregate indoors during periods of bad weather. To test this hypothesis, we combined data from a social contact survey in Belgium with local weather data. In the absence of a previous in-depth weather impact analysis of social contact patterns, we explored the possibilities and identified pitfalls. We found general dominance of day-type (weekend, holiday, working day) over weather conditions, but nonetheless observed an increase in long duration contacts (1 hour) on regular workdays with low temperatures, almost no precipitation and low absolute humidity of the air. Interestingly, these conditions are often assumed to be beneficial for virus survival and transmission. Further research is needed to establish the impact of the weather on social contacts. We recommend that future studies sample over a broad spectrum of weather conditions and day types and include a sufficiently large proportion of holiday periods and weekends. 相似文献
47.
A Roy A Bhardwaj P Datta GC Lander G Cingolani 《Structure (London, England : 1993)》2012,20(8):1403-1413
Packaging of viral genomes into empty procapsids is powered by a large DNA-packaging motor. In most viruses, this machine is composed of a large (L) and a small (S) terminase subunit complexed with a dodecamer of portal protein. Here we describe the 1.75?? crystal structure of the bacteriophage P22 S-terminase in a nonameric conformation. The structure presents a central channel ~23?? in diameter, sufficiently large to accommodate hydrated B-DNA. The last 23 residues of S-terminase are essential for binding to DNA and assembly to L-terminase. Upon binding to its own DNA, S-terminase functions as a specific activator of L-terminase ATPase activity. The DNA-dependent stimulation of ATPase activity thus rationalizes the exclusive specificity of genome-packaging motors for viral DNA in the crowd of host DNA, ensuring fidelity of packaging and avoiding wasteful ATP hydrolysis. This posits?a model for DNA-dependent activation of genome-packaging motors of general interest in virology. 相似文献
48.
49.
50.
Benthic diatoms are dominant primary producers in intertidal marine sediments, which are characterized by widely fluctuating and often extreme light conditions. To cope with sudden increases in light intensity, benthic diatoms display both behavioural and physiological photoprotection mechanisms. Behavioural photoprotection is restricted to raphid pennate diatoms, which possess a raphe system that enables motility and hence positioning in sediment light gradients (e.g. via vertical migration into the sediment). The main physiological photoprotection mechanism is to dissipate excess light energy as heat, measured as Non-Photochemical Quenching (NPQ) of chlorophyll fluorescence. A trade-off between vertical migration and physiological photoprotection (NPQ) in benthic diatoms has been hypothesized before, but this has never been formally tested. We exposed five epipelic diatom species (which move in between sediment particles) and four epipsammic diatom species (which live in close association with individual sand grains) to high light conditions, and characterized both NPQ and the relative magnitude of the migratory response to high light. Our results reveal the absence of a significant downward migratory response in an araphid diatom, but also in several raphid epipsammic diatoms, while all epipelic species showed a significant migratory response upon high light exposure. In all epipsammic species the upregulation of NPQ was rapid and pronounced; NPQ relaxation in low light conditions, however, occurred faster in the araphid diatom, compared with the raphid epipsammic species. In contrast, all epipelic species lacked a strong and flexible NPQ response and showed higher susceptibility to photodamage when not able to migrate. While overall our results support the vertical migration-NPQ trade-off, the lack of strong relationships between the capacity for vertical migration and NPQ within the epipsammic and epipelic groups suggests that other factors as well, such as cell size, substrate type and photoacclimation, may influence photoprotective strategies. 相似文献