全文获取类型
收费全文 | 4266篇 |
免费 | 471篇 |
国内免费 | 393篇 |
出版年
2024年 | 19篇 |
2023年 | 140篇 |
2022年 | 142篇 |
2021年 | 184篇 |
2020年 | 177篇 |
2019年 | 191篇 |
2018年 | 155篇 |
2017年 | 128篇 |
2016年 | 177篇 |
2015年 | 177篇 |
2014年 | 256篇 |
2013年 | 333篇 |
2012年 | 248篇 |
2011年 | 179篇 |
2010年 | 153篇 |
2009年 | 204篇 |
2008年 | 229篇 |
2007年 | 213篇 |
2006年 | 234篇 |
2005年 | 194篇 |
2004年 | 218篇 |
2003年 | 204篇 |
2002年 | 152篇 |
2001年 | 101篇 |
2000年 | 74篇 |
1999年 | 65篇 |
1998年 | 90篇 |
1997年 | 71篇 |
1996年 | 64篇 |
1995年 | 66篇 |
1994年 | 55篇 |
1993年 | 35篇 |
1992年 | 28篇 |
1991年 | 27篇 |
1990年 | 17篇 |
1989年 | 15篇 |
1988年 | 20篇 |
1987年 | 15篇 |
1986年 | 7篇 |
1985年 | 13篇 |
1984年 | 19篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1977年 | 2篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有5130条查询结果,搜索用时 31 毫秒
51.
V. Collura J. Higo J. Garnier 《Protein science : a publication of the Protein Society》1993,2(9):1502-1510
A method is presented to model loops of protein to be used in homology modeling of proteins. This method employs the ESAP program of Higo et al. (Higo, J., Collura, V., & Garnier, J., 1992, Biopolymers 32, 33-43) and is based on a fast Monte Carlo simulation and a simulated annealing algorithm. The method is tested on different loops or peptide segments from immunoglobulin, bovine pancreatic trypsin inhibitor, and bovine trypsin. The predicted structure is obtained from the ensemble average of the coordinates of the Monte Carlo simulation at 300 K, which exhibits the lowest internal energy. The starting conformation of the loop prior to modeling is chosen to be completely extended, and a closing harmonic potential is applied to N, CA, C, and O atoms of the terminal residues. A rigid geometry potential of Robson and Platt (1986, J. Mol. Biol. 188, 259-281) with a united atom representation is used. This we demonstrate to yield a loop structure with good hydrogen bonding and torsion angles in the allowed regions of the Ramachandran map. The average accuracy of the modeling evaluated on the eight modeled loops is 1 A root mean square deviation (rmsd) for the backbone atoms and 2.3 A rmsd for all heavy atoms. 相似文献
52.
Crosslinking mass spectrometry captures protein structures in solution. The crosslinks reveal spatial proximities as distance restraints, but do not easily reveal which of these restraints derive from the same protein conformation. This superposition can be reduced by photo-crosslinking, and adding information from protein structure models, or quantitative crosslinking reveals conformation-specific crosslinks. As a consequence, crosslinking MS has proven useful already in the context of multiple dynamic protein systems. We foresee a breakthrough in the resolution and scale of studying protein dynamics when crosslinks are used to guide deep-learning-based protein modelling. Advances in crosslinking MS, such as photoactivatable crosslinking and in-situ crosslinking, will then reveal protein conformation dynamics in the cellular context, at a pseudo-atomic resolution, and plausibly in a time-resolved manner. 相似文献
53.
In the era of big data, univariate models have widely been used as a workhorse tool for quickly producing marginal estimators; and this is true even when in a high-dimensional dense setting, in which many features are “true,” but weak signals. Genome-wide association studies (GWAS) epitomize this type of setting. Although the GWAS marginal estimator is popular, it has long been criticized for ignoring the correlation structure of genetic variants (i.e., the linkage disequilibrium [LD] pattern). In this paper, we study the effects of LD pattern on the GWAS marginal estimator and investigate whether or not additionally accounting for the LD can improve the prediction accuracy of complex traits. We consider a general high-dimensional dense setting for GWAS and study a class of ridge-type estimators, including the popular marginal estimator and the best linear unbiased prediction (BLUP) estimator as two special cases. We show that the performance of GWAS marginal estimator depends on the LD pattern through the first three moments of its eigenvalue distribution. Furthermore, we uncover that the relative performance of GWAS marginal and BLUP estimators highly depends on the ratio of GWAS sample size over the number of genetic variants. Particularly, our finding reveals that the marginal estimator can easily become near-optimal within this class when the sample size is relatively small, even though it ignores the LD pattern. On the other hand, BLUP estimator has substantially better performance than the marginal estimator as the sample size increases toward the number of genetic variants, which is typically in millions. Therefore, adjusting for the LD (such as in the BLUP) is most needed when GWAS sample size is large. We illustrate the importance of our results by using the simulated data and real GWAS. 相似文献
54.
A rapid method for extraction of cotton (Gossypium spp.) genomic DNA suitable for RFLP or PCR analysis 总被引:13,自引:0,他引:13
Andrew H. Paterson Curt L. Brubaker Jonathan F. Wendel 《Plant Molecular Biology Reporter》1993,11(2):122-127
Extraction of high-quality genomic DNA fromGossypium (cotton) species is difficult due to high levels of polysaccharide, oxidizable quinones, and other interfering substances.
We describe a procedure that consistently permits isolation of cotton genomic DNA of satisfactory size and quality for RFLP
and PCR analysis, as well as for most routine cloning applications. Several antioxidants, phenol-binding reagents, and phenol
oxidase inhibitors are used throughout the procedure, and most polysaccharides are eliminated early in the procedure by isolation
of nuclei. 相似文献
55.
《Journal of molecular biology》2023,435(16):168190
Biomolecular condensates (BMCs) play an important role in the replication of a growing number of viruses, but many important mechanistic details remain to be elucidated. Previously, we demonstrated that the pan-retroviral nucleocapsid (NC) and HIV-1 pr55Gag (Gag) proteins phase separate into condensates, and that HIV-1 protease (PR)-mediated maturation of Gag and Gag-Pol precursor proteins yields self-assembling BMCs that have HIV-1 core architecture. Using biochemical and imaging techniques, we aimed to further characterize the phase separation of HIV-1 Gag by determining which of its intrinsically disordered regions (IDRs) influence the formation of BMCs, and how the HIV-1 viral genomic RNA (gRNA) could influence BMC abundance and size. We found that mutations in the Gag matrix (MA) domain or the NC zinc finger motifs altered condensate number and size in a salt-dependent manner. Gag BMCs were also bimodally influenced by the gRNA, with a condensate-promoting regime at lower protein concentrations and a gel dissolution at higher protein concentrations. Interestingly, incubation of Gag with CD4+ T cell nuclear lysates led to the formation of larger BMCs compared to much smaller ones observed in the presence of cytoplasmic lysates. These findings suggest that the composition and properties of Gag-containing BMCs may be altered by differential association of host factors in nuclear and cytosolic compartments during virus assembly. This study significantly advances our understanding of HIV-1 Gag BMC formation and provides a foundation for future therapeutic targeting of virion assembly. 相似文献
56.
Stella Erdmann Dominic Edelmann Meinhard Kieser 《Biometrical journal. Biometrische Zeitschrift》2023,65(6):2200023
The gold standard for investigating the efficacy of a new therapy is a (pragmatic) randomized controlled trial (RCT). This approach is costly, time-consuming, and not always practicable. At the same time, huge quantities of available patient-level control condition data in analyzable format of (former) RCTs or real-world data (RWD) are neglected. Therefore, alternative study designs are desirable. The design presented here consists of setting up a prediction model for determining treatment effects under the control condition for future patients. When a new treatment is intended to be tested against a control treatment, a single-arm trial for the new therapy is conducted. The treatment effect is then evaluated by comparing the outcomes of the single-arm trial against the predicted outcomes under the control condition. While there are obvious advantages of this design compared to classical RCTs (increased efficiency, lower cost, alleviating participants’ fear of being on control treatment), there are several sources of bias. Our aim is to investigate whether and how such a design—the prediction design—may be used to provide information on treatment effects by leveraging external data sources. For this purpose, we investigated under what assumptions linear prediction models could be used to predict the counterfactual of patients precisely enough to construct a test and an appropriate sample size formula for evaluating the average treatment effect in the population of a new study. A user-friendly R Shiny application (available at: https://web.imbi.uni-heidelberg.de/PredictionDesignR/ ) facilitates the application of the proposed methods, while a real-world application example illustrates them. 相似文献
57.
58.
Thang V. Pham Vinh V. Nguyen Duong Vu Alex A. Henneman Robin A. Richardson Sander R. Piersma Connie R. Jimenez 《Proteomics》2023,23(7-8):2200041
Accurate retention time (RT) prediction is important for spectral library-based analysis in data-independent acquisition mass spectrometry-based proteomics. The deep learning approach has demonstrated superior performance over traditional machine learning methods for this purpose. The transformer architecture is a recent development in deep learning that delivers state-of-the-art performance in many fields such as natural language processing, computer vision, and biology. We assess the performance of the transformer architecture for RT prediction using datasets from five deep learning models Prosit, DeepDIA, AutoRT, DeepPhospho, and AlphaPeptDeep. The experimental results on holdout datasets and independent datasets exhibit state-of-the-art performance of the transformer architecture. The software and evaluation datasets are publicly available for future development in the field. 相似文献
59.
60.
Jing‐Fang Guo Baosheng Wang Zhan‐Lin Liu Jian‐Feng Mao Xiao‐Ru Wang Wei Zhao 《植物分类学报:英文版》2023,61(1):143-156
Endemic species are important components of regional biodiversity and hold the key to understanding local adaptation and evolutionary processes that shape species distributions. This study investigated the biogeographic history of a relict conifer Pinus bungeana Zucc. ex Endl. confined to central China. We examined genetic diversity in P. bungeana using genotyping-by-sequencing and chloroplast and mitochondrial DNA markers. We performed spatial and temporal inference of recent genetic and demographic changes, and dissected the impacts of geography and environmental gradients on population differentiation. We then projected P. bungeana's risk of decline under future climates. We found extremely low nucleotide diversity (average π 0.0014), and strong population structure (global FST 0.234) even at regional scales, reflecting long-term isolation in small populations. The species experienced severe bottlenecks in the early Pliocene and continued to decline in the Pleistocene in the western distribution, whereas the east expanded recently. Local adaptation played a small (8%) but significant role in population diversity. Low genetic diversity in fragmented populations makes the species highly vulnerable to climate change, particularly in marginal and relict populations. We suggest that conservation efforts should focus on enhancing gene pool and population growth through assisted migration within each genetic cluster to reduce the risk of further genetic drift and extinction. 相似文献