全文获取类型
收费全文 | 1146篇 |
免费 | 124篇 |
国内免费 | 18篇 |
专业分类
化学 | 1149篇 |
晶体学 | 3篇 |
力学 | 2篇 |
综合类 | 12篇 |
数学 | 19篇 |
物理学 | 103篇 |
出版年
2024年 | 1篇 |
2023年 | 22篇 |
2022年 | 55篇 |
2021年 | 51篇 |
2020年 | 89篇 |
2019年 | 35篇 |
2018年 | 24篇 |
2017年 | 25篇 |
2016年 | 48篇 |
2015年 | 60篇 |
2014年 | 53篇 |
2013年 | 95篇 |
2012年 | 75篇 |
2011年 | 65篇 |
2010年 | 58篇 |
2009年 | 61篇 |
2008年 | 60篇 |
2007年 | 75篇 |
2006年 | 73篇 |
2005年 | 43篇 |
2004年 | 38篇 |
2003年 | 25篇 |
2002年 | 33篇 |
2001年 | 10篇 |
2000年 | 19篇 |
1999年 | 24篇 |
1998年 | 10篇 |
1997年 | 14篇 |
1996年 | 7篇 |
1995年 | 14篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1985年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有1288条查询结果,搜索用时 15 毫秒
151.
A novel protocol for all‐atom RNA tertiary structure prediction is presented that uses restrained molecular mechanics and simulated annealing. The restraints are from secondary structure, covariation analysis, coaxial stacking predictions for helices in junctions, and, when available, cross‐linking data. Results are demonstrated on the Alu domain of the mammalian signal recognition particle RNA, the Saccharomyces cerevisiae phenylalanine tRNA, the hammerhead ribozyme, the hepatitis C virus internal ribosomal entry site, and the P4–P6 domain of the Tetrahymena thermophila group I intron. The predicted structure is selected from a pool of decoy structures with a score that maximizes radius of gyration and base–base contacts, which was empirically found to select higher quality decoys. This simple ab initio approach is sufficient to make good predictions of the structure of RNAs compared to current crystal structures using both root mean square deviation and the accuracy of base–base contacts. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011 相似文献
152.
Changing ocean-carbonate chemistry caused by oceanic uptake of anthropogenic atmospheric carbon dioxide leads to the formation of carbonic acid, thus lowering the pH of the sea with predictions of a decrease from current levels at 8.15 to 7.82 by the end of the century. The exact measurement of subtle pH changes in seawater over time presents significant analytical challenges, as the equilibrium constants are governed by water temperature and pressure, salinity effects, and the existence of other ionic species in seawater.Here, we review these challenges and how pH also affects dissolved inorganic and organic chemicals that affect biological systems. This includes toxic compounds (xenobiotics) as well as chemicals that are beneficial for marine organisms, such as the chemical signals (i.e. pheromones) that are utilized to coordinate animal behavior. We review how combining analytical, molecular and biochemical tools can lead to the development of biosensors to detect pH effects to enable predictive modeling of the ecological consequences of ocean acidification. 相似文献
153.
Gomes AG Azevedo AM Aires-Barros MR Prazeres DM 《Journal of chromatography. A》2011,1218(48):8629-8637
Plasmid DNA (pDNA) is purified directly from alkaline lysis-derived Escherichia coli (E. coli) lysates by phenyl boronate (PB) chromatography. The method explores the ability of PB ligands to bind covalently, but reversibly, to cis-diol-containing impurities like RNA and lipopolysaccharides (LPS), leaving pDNA in solution. In spite of this specificity, cis-diol free species like proteins and genomic DNA (gDNA) are also removed. This is a major advantage since the process is designed to keep the target pDNA from binding. The focus of this paper is on the study of the secondary interactions between the impurities (RNA, gDNA, proteins, LPS) in a pDNA-containing lysate and 3-amino PB controlled pore glass (CPG) matrices. Runs were designed to evaluate the role of adsorption buffer composition, feed type (pH, salt content), CPG matrix and sample pretreatment (RNase A, isopropanol precipitation). Water was chosen as the adsorption buffer over MgCl(2) solutions since it maximised pDNA yield (96.2±4.9%) and protein removal (61.3±3.0%), while providing for a substantial removal of RNA (65.5±3.5%) and gDNA (44.7±14.1%). Although the use of pH 3.5 maximised removal of impurities (~75%), the best compromise between plasmid yield (~96%) and RNA clearance (~60-70%) was obtained for a pH of 5.2. Plasmid yield was maximal (>96%) when the concentration of acetate and potassium ions in the incoming lysate feed were 1.7 M and 1.0 M, respectively. The pre-treatment of lysates with RNase A deteriorated the performance since the resulting oligoribonucleotides lack the cis-diol group at their 3' termini. Overall, the results support the idea that charge transfer interactions between the boron atom at acidic pH and electron donor groups in the aromatic bases of nucleic acids and side residues of proteins are responsible for the non-specific removal of gDNA, RNA and proteins. 相似文献
154.
Cyclooxygenase-2 (COX-2) is an important enzyme in inflammation. In this study, we investigated the underlying molecular mechanism of the synergistic effect of rottlerin on interleukin1β (IL-1β)-induced COX-2 expression in MDA-MB-231 human breast cancer cell line. Treatment with rottlerin enhanced IL-1β-induced COX-2 expression at both the protein and mRNA levels. Combined treatment with rottlerin and IL-1β significantly induced COX-2 expression, at least in part, through the enhancement of COX-2 mRNA stability. In addition, rottlerin and IL-1β treatment drove sustained activation of p38 Mitogen-activated protein kinase (MAPK), which is involved in induced COX-2 expression. Also, a pharmacological inhibitor of p38 MAPK (SB 203580) and transient transfection with inactive p38 MAPK inhibited rottlerin and IL-1β-induced COX-2 upregulation. However, suppression of protein kinase C δ (PKC δ) expression by siRNA or overexpression of dominant-negative PKC δ (DN-PKC-δ) did not abrogate the rottlerin plus IL-1β-induced COX-2 expression. Furthermore, rottlerin also enhanced tumor necrosis factor-α (TNF-α), phorbol myristate acetate (PMA), and lipopolysaccharide (LPS)-induced COX-2 expression. Taken together, our results suggest that rottlerin causes IL-1β-induced COX-2 upregulation through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells. 相似文献
155.
156.
Lluís Guijarro lvaro Martínez-Camarena Javier U. Chicote Antonio García-Espaa Enrique García-Espaa Mario Incln Begoa Verdejo Jorge Gonzlez-García 《Molecules (Basel, Switzerland)》2021,26(13)
Nucleic acids are essential biomolecules in living systems and represent one of the main targets of chemists, biophysics, biologists, and nanotechnologists. New small molecules are continuously developed to target the duplex (ds) structure of DNA and, most recently, RNA to be used as therapeutics and/or biological tools. Stimuli-triggered systems can promote and hamper the interaction to biomolecules through external stimuli such as light and metal coordination. In this work, we report on the interaction with ds-DNA and ds-RNA of two aza-macrocycles able to coordinate Zn2+ metal ions and form binuclear complexes. The interaction of the aza-macrocycles and the Zn2+ metal complexes with duplex DNA and RNA was studied using UV thermal and fluorescence indicator displacement assays in combination with theoretical studies. Both ligands show a high affinity for ds-DNA/RNA and selectivity for ds-RNA. The ability to interact with these duplexes is blocked upon Zn2+ coordination, which was confirmed by the low variation in the melting temperature and poor displacement of the fluorescent dye from the ds-DNA/RNA. Cell viability assays show a decrease in the cytotoxicity of the metal complexes in comparison with the free ligands, which can be associated with the observed binding to the nucleic acids. 相似文献
157.
The work is devoted to the study of the complementarity of the electronic structures of the ligands and SARS-CoV-2 RNA-dependent RNA polymerase. The research methodology was based on determining of 3D maps of electron densities of complexes using an original quantum free-orbital AlteQ approach. We observed a positive relationship between the parameters of the electronic structure of the enzyme and ligands. A complementarity factor of the enzyme-ligand complexes has been proposed. The console applications of the AlteQ complementarity assessment for Windows and Linux (alteq_map_enzyme_ligand_4_win.exe and alteq_map_enzyme_ligand_4_linux) are available for free at the ChemoSophia webpage. 相似文献
158.
159.
160.
Y. Kafri D. Mukamel L. Peliti 《The European Physical Journal B - Condensed Matter and Complex Systems》2002,27(1):135-146
Existing experimental studies of the thermal denaturation of DNA yield sharp steps in the melting curve suggesting that the
melting transition is first order. This transition has been theoretically studied since the early sixties, mostly within an
approach in which the microscopic configurations of a DNA molecule consist of an alternating sequence of non-interacting bound
segments and denaturated loops. Studies of these models neglect the repulsive, self-avoiding, interaction between different
loops and segments and have invariably yielded continuous denaturation transitions. In the present study we take into account
in an approximate way the excluded-volume interaction between denaturated loops and the rest of the chain. This is done by
exploiting recent results on scaling properties of polymer networks of arbitrary topology. We also ignore the heterogeneity
of the polymer. We obtain a first-order melting transition in d = 2 dimensions and above, consistent with the experimental results. We also consider within our approach the unzipping transition,
which takes place when the two DNA strands are pulled apart by an external force acting on one end. We find that the under
equilibrium condition the unzipping transition is also first order. Although the denaturation and unzipping transitions are
thermodynamically first order, they do exhibit critical fluctuations in some of their properties. For instance, the loop size
distribution decays algebraically at the transition and the length of the denaturated end segment diverges as the transition
is approached. We evaluate these critical properties within our approach.
Received 21 August 2001 and Received in final form 26 January 2002 相似文献