全文获取类型
收费全文 | 184篇 |
免费 | 7篇 |
国内免费 | 56篇 |
专业分类
化学 | 228篇 |
晶体学 | 1篇 |
力学 | 1篇 |
数学 | 1篇 |
物理学 | 16篇 |
出版年
2024年 | 1篇 |
2023年 | 8篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 7篇 |
2019年 | 7篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 9篇 |
2014年 | 4篇 |
2013年 | 21篇 |
2012年 | 14篇 |
2011年 | 12篇 |
2010年 | 9篇 |
2009年 | 21篇 |
2008年 | 19篇 |
2007年 | 13篇 |
2006年 | 15篇 |
2005年 | 11篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1987年 | 1篇 |
排序方式: 共有247条查询结果,搜索用时 296 毫秒
91.
针对组织蛋白酶K(Cat K)的活性位点的化学结构特征设计合成了一系列拟肽腈类抑制剂, 并检测了其抑制效果, 得到了高效且具有较高选择性的抑制剂(其中抑制剂b和f对Cat K的抑制常数Ki值分别为15.9和19.1 nmol/L). 构效关系分析表明, P2与P3位连接部分以及P3基团的结构不同可使其抑制效果产生100倍以上的差异. 相似文献
92.
Rafael Gozalbes Silvia Mosulén Rodrigo J. Carbajo Antonio Pineda-Lucena 《Journal of computer-aided molecular design》2009,23(8):555-569
A combined strategy based on the development of pharmacophore hypotheses and NMR approaches is reported for the identification
of novel inhibitors of heparanase, a key enzyme involved in tumor metastasis through the remodeling of the subepithelial and
subendothelial basement membranes, resulting in the dissemination of metastatic cancer cells. Several pharmacophore hypotheses
were initially developed from the most active heparanase inhibitors known to date and, after their application to a pool of
27 known heparanase inhibitors and a database of 1,120 compounds approved by the FDA, a four-point pharmacophore model was
selected as the most predictive. This model was subsequently applied to a database of 686 chemical fragments, and a subset
of 100 fragments accomplishing completely or partially the four-point model was selected to perform nuclear magnetic resonance
experiments to validate the hypothesis. The experimental studies confirmed the reliability of our pharmacophore model, its
applicability to in silico databases in order to reduce the number of compounds to be experimentally screened, and the possibility
of generating fragment libraries enriched in heparanase inhibitors.
Rafael Gozalbes and Silvia Mosulén contributed equally to this work. 相似文献
93.
Approval of bortezomib has validated ubiquitin-proteasome pathway as an important target for treatment of haematological malignancies. However, clinical shortcomings of bortezomib, a covalent peptide proteasome inhibitor, has prompted a paradigm shift in anti-proteasome drug discovery towards development of non-peptidic inhibitors and targeting of upstream ubiquitin system which has drawn traction for interdisciplinary forays. It is being widely recognized that natural products provide valuable leads in the discovery of potent, chemically diverse, non-peptidic inhibitors of 20S proteasome and of key enzymes involved in ubiquitination machinery. As a result, total synthesis of natural, non-peptidic inhibitors of ubiquitin-proteasome pathway has emerged as a critical interlink between organic synthesis, medicinal chemistry, biochemical profiling and drug discovery. An up-to-date account of contextual synthetic challenges, strategies and accomplishments as well as mapping of the chemical diversity space around the natural scaffolds has been captured in this review. 相似文献
94.
《Arabian Journal of Chemistry》2019,12(7):1024-1034
The corrosion inhibition characteristics of Sulfadoxine plus Pyrimethamine (S&P) was evaluated and compared with the inhibition performance of an industrial corrosion inhibitor (S-Ind) under anaerobic condition. Modified gravimetric and electrochemical techniques were used. The corrosion inhibition efficiencies of both S&P and S-Ind were comparable for all the techniques applied. S&P gave slightly higher inhibition efficiency, while S-Ind gave a more steady corrosion protection. The corrosion inhibition efficiencies increased with increased concentration of both substances. The polarization curves showed mixed inhibition behavior for both S&P and S-Ind. A mechanism of chemisorption was proposed for the adsorption of S&P and S-Ind on pipeline steel surface, while the negative Gibbs free energy of adsorption values indicates a spontaneous adsorption process. The adsorption characteristics of the inhibitors were fitted into Langmuir adsorption isotherm. 相似文献
95.
The interaction of benzotriazole (BTAH) with the surface of a corroding copper–nickel alloy in a sulfide polluted salt solution reveals a change in its role from an inhibitor to a promoter of localized corrosion as its concentration changes. A concentration of BTAH ≥5 × 10−4 M inhibits the corrosion reaction in both the polluted and the unpolluted media. On the other hand, a concentration of 10−4 M BTAH promotes the localized corrosion of the alloy in the polluted medium while it acts as an inhibitor in the unpolluted salt solution. This finding is substantiated by measurements of mass loss and current transients and examination of the surface by SEM microscopy. 相似文献
96.
以分子对接法进行MDL/ACD三维数据库搜寻所得到的大量结构信息为指导, 从中选取部分酰胺类小分子进行化学合成和结构表征. 生物活性测试结果表明, 设计合成的8个酰胺类化合物在200 μg/mL浓度下对水稻KARI酶具有不同程度的抑制活性, 化合物1和6的抑制率可达到57.4%和48.1%. 部分化合物在100 μg/mL浓度下对双子叶植物油菜的胚根和单子叶植物稗草的茎叶的抑制活性较为显著, 化合物1和6对油菜胚根生长抑制率分别为52.0%和72.6%, 其与KARI酶体外(in vitro)抑制活性具有一定的相关性. 这些酰胺类化合物可作为KARI酶抑制剂为后续分子设计提供借鉴. 相似文献
97.
Inhibition Mechanism of Hydroxyproline-like Small Inhibitors to Disorder HIF-VHL Interaction by Molecular Dynamic Simulations and Binding Free Energy Calculations 下载免费PDF全文
Mingsong Shi Xin Zhou Yao Cai Penghui Li Dengxue Qin Xinrong Yan Meng Du Shuo Li Dingguo Xu 《化学物理学报(中文版)》2021,34(6):814-824
Protein-protein interactions are vital for a wide range of biological processes. The interactions between the hypoxia-inducible factor and von Hippel Lindau (VHL) are attractive drug targets for ischemic heart disease. In order to disrupt this interaction, the strategy to target VHL binding site using a hydroxyproline-like (pro-like) small molecule has been reported. In this study, we focused on the inhibition mechanism between the pro-like inhibitors and the VHL protein, which were investigated via molecular dynamics simulations and binding free energy calculations. It was found that pro-like inhibitors showed a strong binding affinity toward VHL. Binding free energy calculations and free energy decompositions suggested that the modification of various regions of pro-like inhibitors may provide useful information for future drug design. 相似文献
98.
Efficient procedures have been developed for the stereospecific synthesis of Angiotensin-converting enzyme inhibitor, Enalapril. The starting material, (R)-2-hydroxy-4-phenylbutyronitrile, is prepared from lipase-catalyzed acetylation. This process is useful for multigram-scale synthesis. 相似文献
99.
Zhao R Fanga C Yu X Liu Y Luo J Shangguan D Xiong S Su T Liu G 《Journal of chromatography. A》2005,1064(1):59-66
The affinity inhibitor of fusion peptide of influenza A virus has been studied using a combination of high-performance affinity chromatography (HPAC) and combinatorial peptide libraries. Fusion peptide (FP) (1-11) of influenza A virus was used as the affinity ligand and immobilized onto the poly(glycidyl methacrylate) (PGMA) beads. Positional scanning peptide libraries based on antisense peptide strategy and extended peptide libraries were designed and synthesized. The screening was carried out at acidic pH (5.5) in order to imitate the environment of virus fusion. A hendecapeptide FHRKKGRGKHK was identified to have a strong affinity to the FP (1-11). The dissociation constant of the complex of the hendecapeptide and the FP (1-11) is 3.10 x 10(-6) mol l(-1) in a physiological buffer condition. The polypeptide has a fairly inhibitory effect on three different strains of influenza A virus H1N1 subtype. 相似文献
100.
研究了一类具有抑制剂和质载的非均匀恒化器模型.首先,采用锥映射上不动点指标理论得到了物种共存的充分条件.然后,根据度理论及摄动理论,研究了模型正平衡态解的唯一性和稳定性.结果表明当抑制剂的影响充分大时,模型存在唯一的渐近稳定的共存解.最后,利用比较原理和一致持续理论研究了系统的长时行为,并采用数值模拟的方法对所得结论进行了验证和补充. 相似文献