全文获取类型
收费全文 | 1241篇 |
免费 | 137篇 |
国内免费 | 114篇 |
专业分类
1492篇 |
出版年
2024年 | 2篇 |
2023年 | 23篇 |
2022年 | 30篇 |
2021年 | 36篇 |
2020年 | 33篇 |
2019年 | 43篇 |
2018年 | 48篇 |
2017年 | 45篇 |
2016年 | 49篇 |
2015年 | 55篇 |
2014年 | 64篇 |
2013年 | 105篇 |
2012年 | 48篇 |
2011年 | 41篇 |
2010年 | 54篇 |
2009年 | 75篇 |
2008年 | 81篇 |
2007年 | 75篇 |
2006年 | 66篇 |
2005年 | 76篇 |
2004年 | 63篇 |
2003年 | 48篇 |
2002年 | 38篇 |
2001年 | 33篇 |
2000年 | 39篇 |
1999年 | 27篇 |
1998年 | 25篇 |
1997年 | 26篇 |
1996年 | 17篇 |
1995年 | 21篇 |
1994年 | 15篇 |
1993年 | 10篇 |
1992年 | 12篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 14篇 |
1988年 | 6篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 2篇 |
排序方式: 共有1492条查询结果,搜索用时 15 毫秒
81.
82.
The Escherichia coli metabolome has been characterised using the two-dimensional structures of 745 metabolites, obtained from the EcoCyc and KEGG databases. Physicochemical properties of the metabolome have been calculated to provide an overview of this set of cognate ligands. A library of fragments commonly found among these molecules has been employed to reveal the main constituents of metabolites, and to assist a broad classification of the metabolome into biochemically relevant classes. Fragment-based fingerprints reveal the metabolome as a continuum in the two-dimensional structural space, where clusters of molecules sharing similar scaffolds can be identified, but are generally overlapping. Nucleotide, carbohydrate and amino acid-like molecules are the most prominent, but at high levels of similarity, a more detailed classification is possible. Classification schemes for the metabolome are a promising tool for understanding the chemical diversity of the metabolome. When used in conjunction with existing classifications of the proteome, they can help to elucidate the binding preferences and promiscuity of proteins and their cognate substrates. 相似文献
83.
韩世辉 《中国科学C辑(英文版)》2003,46(2):113-126
Palmer and Rock proposed that uniform connectedness (UC) occurs prior to classical Gestalt factors to define the primitive units for visual perception. Han, Humphreys and Chen, however, found that grouping by proximity can take place as quickly as that based on UC in a letter discrimination task. The present study employed a letter detection task to examine the relationship between UC and proximity grouping in 3 experiments. We showed that reaction times to targets defined by proximity or UC were equally fast when one or two global objects were presented in the visual field. However, as the number of global objects was increased, responses were faster to targets defined by UC than to targets defined by proximity. In addition, the advantage of UC over proximity was not affected by the space between global objects. The results suggest that UC was more effective than proximity in forming perceptual units under multiple object conditions. Possible reasons for this finding are discussed. 相似文献
84.
Background
Chondroitin sulfate proteoglycans (CSPGs) are principal pericellular and extracellular components that form regulatory milieu involving numerous biological and pathophysiological phenomena. Diverse functions of CSPGs can be mainly attributed to structural variability of their polysaccharide moieties, chondroitin sulfate glycosaminoglycans (CS-GAG). Comprehensive understanding of the regulatory mechanisms for CS biosynthesis and its catabolic processes is required in order to understand those functions.Scope of review
Here, we focus on recent advances in the study of enzymatic regulatory pathways for CS biosynthesis including successive modification/degradation, distinct CS functions, and disease phenotypes that have been revealed by perturbation of the respective enzymes in vitro and in vivo.Major conclusions
Fine-tuned machineries for CS production/degradation are crucial for the functional expression of CS chains in developmental and pathophysiological processes.General significance
Control of enzymes responsible for CS biosynthesis/catabolism is a potential target for therapeutic intervention for the CS-associated disorders. 相似文献85.
86.
87.
Rajathei David Mary Mani K Saravanan 《Journal of biomolecular structure & dynamics》2013,31(3):534-551
Domains are the main structural and functional units of larger proteins. They tend to be contiguous in primary structure and can fold and function independently. It has been observed that 10–20% of all encoded proteins contain duplicated domains and the average pairwise sequence identity between them is usually low. In the present study, we have analyzed the structural similarity between domain repeats of proteins with known structures available in the Protein Data Bank using structure-based inter-residue interaction measures such as the number of long-range contacts, surrounding hydrophobicity, and pairwise interaction energy. We used RADAR program for detecting the repeats in a protein sequence which were further validated using Pfam domain assignments. The sequence identity between the repeats in domains ranges from 20 to 40% and their secondary structural elements are well conserved. The number of long-range contacts, surrounding hydrophobicity calculations and pairwise interaction energy of the domain repeats clearly reveal the conservation of 3-D structure environment in the repeats of domains. The proportions of mainchain–mainchain hydrogen bonds and hydrophobic interactions are also highly conserved between the repeats. The present study has suggested that the computation of these structure-based parameters will give better clues about the tertiary environment of the repeats in domains. The folding rates of individual domains in the repeats predicted using the long-range order parameter indicate that the predicted folding rates correlate well with most of the experimentally observed folding rates for the analyzed independently folded domains. 相似文献
88.
《Bioscience, biotechnology, and biochemistry》2013,77(11):2112-2118
A novel method combining imaging techniques and fluorescence fingerprint (FF) data measurement was developed to visualize the distributions of gluten and starch in dough without any preprocessing. Fluorescence images of thin sections of gluten, starch, and dough were acquired under 63 different combinations of excitation and emission wavelengths, resulting in a set of data consisting of the FF data for each pixel. Cosine similarity values between the FF of each pixel in the dough and those of gluten and starch were calculated. Each pixel was colored according to the cosine similarity value to obtain a pseudo-color image showing the distributions of gluten and starch. The dough sample was then fluorescently stained for gluten and starch. The stained image showed patterns similar to the pseudo-color FF image, validating the effectiveness of the FF imaging method. The method proved to be a powerful visualization tool, applicable in fields other than food technology. 相似文献
89.
《MABS-AUSTIN》2013,5(6):1474-1485
CTLA4-Ig is a highly glycosylated therapeutic fusion protein that contains multiple N- and O-glycosylation sites. Glycosylation plays a vital role in protein solubility, stability, serum half-life, activity, and immunogenicity. For a CTLA4-Ig biosimilar development program, comparative analytical data, especially the glycosylation data, can influence decisions about the type and amount of animal and clinical data needed to establish biosimilarity. Because of the limited clinical experience with biosimilars before approval, a comprehensive level of knowledge about the biosimilar candidates is needed to achieve subsequent development. Liquid chromatography-mass spectrometry (LC–MS) is a versatile technique for characterizing N- and O-glycosylation modification of recombinant therapeutic proteins, including 3 levels: intact protein analysis, peptide mapping analysis, and released glycans analysis. In this report, an in-depth characterization of glycosylation of a candidate biosimilar was carried out using a systematic approach: N- and O-linked glycans were identified and electron-transfer dissociation was then used to pinpoint the 4 occupied O-glycosylation sites for the first time. As the results show, the approach provides a set of routine tools that combine accurate intact mass measurement, peptide mapping, and released glycan profiling. This approach can be used to comprehensively research a candidate biosimilar Fc-fusion protein and provides a basis for future studies addressing the similarity of CTLA4-Ig biosimilars. 相似文献
90.
The HIV-1 envelope glycoprotein gp41 fusion intermediate is a promising drug target for inhibiting viral entry. However, drug development has been impeded by challenges inherent in mediating the underlying protein–protein interaction. Here we report on the identification of fragments that bind to a C-terminal sub-pocket adjacent to the well-known hydrophobic pocket on the NHR coiled coil. Using a specifically designed assay and ligand-based NMR screening of a fragment library, we identified a thioenylaminopyrazole compound with a dissociation constant of ~500 μM. Interaction with the C-terminal sub-pocket was confirmed by paramagnetic relaxation enhancement NMR experiments, which also yielded the binding mode. Shape-based similarity searching detected additional phenylpyrazole and phenyltriazole fragments within the library, enriching the hit rate over random screening, and revealing molecular features required for activity. Discovery of the novel scaffolds and binding mechanism suggests avenues for extending the interaction surface and improving the potency of a hydrophobic pocket binding inhibitor. 相似文献