全文获取类型
收费全文 | 1316篇 |
免费 | 86篇 |
国内免费 | 1篇 |
出版年
2023年 | 7篇 |
2022年 | 12篇 |
2021年 | 22篇 |
2020年 | 24篇 |
2019年 | 11篇 |
2018年 | 22篇 |
2017年 | 18篇 |
2016年 | 32篇 |
2015年 | 40篇 |
2014年 | 75篇 |
2013年 | 74篇 |
2012年 | 113篇 |
2011年 | 102篇 |
2010年 | 60篇 |
2009年 | 53篇 |
2008年 | 88篇 |
2007年 | 109篇 |
2006年 | 102篇 |
2005年 | 86篇 |
2004年 | 75篇 |
2003年 | 77篇 |
2002年 | 73篇 |
2001年 | 11篇 |
2000年 | 14篇 |
1999年 | 17篇 |
1998年 | 12篇 |
1997年 | 10篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1983年 | 4篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1965年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有1403条查询结果,搜索用时 31 毫秒
1.
Jonathan D. Nickels Joseph E. Curtis Hugh O’Neill Alexei P. Sokolov 《Journal of biological physics》2012,38(3):497-505
Recent studies have discovered strong differences between the dynamics of nucleic acids (RNA and DNA) and proteins, especially at low hydration and low temperatures. This difference is caused primarily by dynamics of methyl groups that are abundant in proteins, but are absent or very rare in RNA and DNA. In this paper, we present a hypothesis regarding the role of methyl groups as intrinsic plasticizers in proteins and their evolutionary selection to facilitate protein dynamics and activity. We demonstrate the profound effect methyl groups have on protein dynamics relative to nucleic acid dynamics, and note the apparent correlation of methyl group content in protein classes and their need for molecular flexibility. Moreover, we note the fastest methyl groups of some enzymes appear around dynamical centers such as hinges or active sites. Methyl groups are also of tremendous importance from a hydrophobicity/folding/entropy perspective. These significant roles, however, complement our hypothesis rather than preclude the recognition of methyl groups in the dynamics and evolution of biomolecules. 相似文献
2.
Daisuke Hirata Alexei V. Abramov Gennady F. Baryshnikov Ryuichi Masuda 《Biological journal of the Linnean Society. Linnean Society of London》2014,111(3):627-635
Sequence analyses of the complete brown bear, Ursus arctos, mitochondrial DNA (mtDNA) genome have detected scattered single nucleotide polymorphisms (SNPs) that define distinct mtDNA haplogroups in phylogeographical studies. The degraded DNA in historical samples, such as stuffed or excavated specimens, however, is often not suitable for sequence analyses. To address this problem, we developed an amplified product length polymorphism (APLP) analysis for mtDNA‐haplogrouping U. arctos specimens by detecting haplogroup‐specific SNPs. We verified the validity and utility of this method by analysing up to 170‐year‐old skin samples from U. arctos specimens collected widely across continental Eurasia. We detected some of the same haplogroups as those occurring in eastern Hokkaido (Japan) and eastern Alaska in continental Eurasia (the Altai and the Caucasus). Our results show that U. arctos in eastern Hokkaido and eastern Alaska descended from a common ancestor in continental Eurasia, and suggest that U. arctos occupied several refugia in southern Asia during the Last Glacial Maximum. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 111 , 627–635. 相似文献
3.
4.
5.
6.
Vytas K. Švedas Alexei L. Margolin Ilya V. Berezin 《Enzyme and microbial technology》1980,2(2):138-144
The equilibrium constants and the respective standard Gibbs energy changes for hydrolysis of some β-lactam antibiotics have been determined. Native and immobilized penicillin amidase (EC 3.5.1.11) from Escherichia coli has been used as a catalyst. The values of standard Gibbs energy changes corresponding to the pH-independent product of equilibrium concentrations (ΔG0c = ? RT ln Kc) have been calculated. The differences in the structure of the antibiotics nucleus hardly ever affect the value of the pH-independent component of the standard Gibbs energy change (ΔG0c) and value of apparent standard Gibbs energy change at a fixed pH (ΔG0′c). At the same time, the value of ΔG0c is more sensitive to the structure of the acyl moiety of the antibiotic; when ampicillin is used instead of benzylpenicillin, ΔG0c increases by ~6.3 kJ mol?1 (1.5 kcal mol?1). pH-dependences of the apparent standard Gibbs energy changes for hydrolysis of β-lactam antibiotics have been calculated. The pH-dependences of ΔG0′c for hydrolysis of all β-lactam antibiotics have a similar pattern. The thermodynamic pH optimum of the synthesis of these compounds is in the acid pH range (pH < 5.0). The breakage of the β-lactam ring leads to a sharp decrease in the ΔG0′c value and a change in the pattern of the pH-dependence. For example, at pH 5.0 ΔG0′c decreases from 14.4 kJ mol?1 for benzylpenicillin to ?1.45 kJ mol?1 for benzylpenicilloic acid. The reason for these changes is mainly a considerable increase in the pK of the amino group of the nucleus of the antibiotic and, as a consequence, a decrease in the component of standard Gibbs energy change, corresponding to the ionization of the system. The thermodynamic potentials of the enzymatic synthesis of semisynthetic penicillins and cephalosporins on the basis of both free acids and their derivatives (N-acylated amino acids, esters) are discussed. It is shown that with esters of the acids, a high yield of the antibiotic can, in principle, be achieved at higher pH values. 相似文献
7.
Boris Yu. Zaslavsky Anna A. Borovskaya Alevtina K. Lavrinenko Alexei Yu. Lisichkin Yurii A. Davidovich Sergei V. Rogozhin 《Chemistry and physics of lipids》1980,26(1):49-55
The lytic action of several homologous series of surfactants including N-acyl derivatives of the Na-salt of amino acids on the egg lecithin multilamellar liposomes was examined. The affinity for the lipid membrane and the solubilising capacity of the agents were estimated. The contribution of a CH2 group and that of the polar head group of surfactants to the free energy of the agent's binding to the membrane were evaluated. The results obtained indicate that the contribution of a CH2 group to the free binding energy depends on the nature of the surfactants' head group. This dependence is attributed to either various localisation of the agent's molecules in the lipid bilayer or to different properties of the agent's hydrocarbon tails. The contributions of the head groups of the surfactants are assumed to reflect the affinity of these head groups for the lecithin polar head group at the membrane interface. The results obtained indicate some degree of specificity involved in the interactions of the head groups. 相似文献
8.
Population Ecology - Female deermice housed from weaning with groups of five females, five males or five males plus five females had significantly smaller uteri at 35–38 days of age compared... 相似文献
9.
Respiratory complex I couples the transfer of electrons from NADH to ubiquinone and the translocation of protons across the mitochondrial membrane. A detailed understanding of the midpoint reduction potentials (Em) of each redox center and the factors which influence those potentials are critical in the elucidation of the mechanism of electron transfer in this enzyme. We present accurate electrostatic interaction energies for the iron-sulfur (FeS) clusters of complex I to facilitate the development of models and the interpretation of experiments in connection to electron transfer (ET) in this enzyme. To calculate redox titration curves for the FeS clusters it is necessary to include interactions between clusters, which in turn can be used to refine Em values and validate spectroscopic assignments of each cluster. Calculated titration curves for clusters N4, N5, and N6a are discussed. Furthermore, we present some initial findings on the electrostatics of the redox centers of complex I under the influence of externally applied membrane potentials. A means of determining the location of the FeS cofactors within the holo-complex based on electrostatic arguments is proposed. A simple electrostatic model of the protein/membrane system is examined to illustrate the viability of our hypothesis. 相似文献
10.
Victoria A. Hassebroek Hyewon Park Nootan Pandey Brooklyn T. Lerbakken Vasilisa Aksenova Alexei Arnaoutov Mary Dasso Yoshiaki Azuma 《Molecular biology of the cell》2020,31(23):2537
Proper chromosome segregation is essential for faithful cell division and if not maintained results in defective cell function caused by the abnormal distribution of genetic information. Polo-like kinase 1–interacting checkpoint helicase (PICH) is a DNA translocase essential for chromosome bridge resolution during mitosis. Its function in resolving chromosome bridges requires both DNA translocase activity and ability to bind chromosomal proteins modified by the small ubiquitin-like modifier (SUMO). However, it is unclear how these activities cooperate to resolve chromosome bridges. Here, we show that PICH specifically disperses SUMO2/3 foci on mitotic chromosomes. This PICH function is apparent toward SUMOylated topoisomerase IIα (TopoIIα) after inhibition of TopoIIα by ICRF-193. Conditional depletion of PICH using the auxin-inducible degron (AID) system resulted in the retention of SUMO2/3-modified chromosomal proteins, including TopoIIα, indicating that PICH functions to reduce the association of these proteins with chromosomes. Replacement of PICH with its translocase-deficient mutants led to increased SUMO2/3 foci on chromosomes, suggesting that the reduction of SUMO2/3 foci requires the remodeling activity of PICH. In vitro assays showed that PICH specifically attenuates SUMOylated TopoIIα activity using its SUMO-binding ability. Taking the results together, we propose a novel function of PICH in remodeling SUMOylated proteins to ensure faithful chromosome segregation. 相似文献