全文获取类型
收费全文 | 188篇 |
免费 | 16篇 |
国内免费 | 50篇 |
专业分类
化学 | 231篇 |
晶体学 | 2篇 |
综合类 | 4篇 |
数学 | 1篇 |
物理学 | 16篇 |
出版年
2023年 | 4篇 |
2022年 | 2篇 |
2021年 | 14篇 |
2020年 | 7篇 |
2019年 | 9篇 |
2018年 | 11篇 |
2017年 | 8篇 |
2016年 | 6篇 |
2015年 | 14篇 |
2014年 | 11篇 |
2013年 | 23篇 |
2012年 | 9篇 |
2011年 | 13篇 |
2010年 | 7篇 |
2009年 | 11篇 |
2008年 | 16篇 |
2007年 | 16篇 |
2006年 | 13篇 |
2005年 | 5篇 |
2004年 | 10篇 |
2003年 | 10篇 |
2002年 | 6篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1979年 | 1篇 |
排序方式: 共有254条查询结果,搜索用时 15 毫秒
71.
72.
Oligomers of leucine, methionine, phenylalanine, and tyrosine were prepared enzymatically (using papain) from the respective methyl esters, with yields ranging from 51–96%. The effect of pH, buffer and salt concentration, and addition of alcohol on the oligomerization of leucine methyl ester was examined. The limits and potentialities of the enzymatic reaction as a method for obtaining monodisperse oligomers are discussed. 相似文献
73.
Takakusa H Kikuchi K Urano Y Kojima H Nagano T 《Chemistry (Weinheim an der Bergstrasse, Germany)》2003,9(7):1479-1485
A ratiometric measurement, namely, simultaneous recording of the fluorescence intensities at two wavelengths and calculation of their ratio, allows greater precision than measurements at a single wavelength, and is suitable for cellular imaging studies. Here we describe a novel method of designing probes for ratiometric measurement of hydrolytic enzyme activity based on switching of fluorescence resonance energy transfer (FRET). This method employs fluorescent probes with a 3'-O,6'-O-protected fluorescein acceptor linked to a coumarin donor through a linker moiety. As there is no spectral overlap integral between the coumarin emission and fluorescein absorption, the fluorescein moiety cannot accept the excitation energy of the donor moiety and the donor fluorescence can be observed. After cleavage of the protective groups by hydrolytic enzymes, the fluorescein moiety shows a strong absorption in the coumarin emission region, and then acceptor fluorescence due to FRET is observed. Based on this mechanism, we have developed novel ratiometric fluorescent probes (1-3) for protein tyrosine phosphatase (PTP) activity. They exhibit a large shift in their emission wavelength after reaction with PTPs. The fluorescence quenching problem that usually occurs with FRET probes is overcome by using the coumarin-cyclohexane-fluorescein FRET cassette moiety, in which close contact of the two dyes is hindered. After study of their chemical and kinetic properties, we have concluded that compounds 1 and 2 bearing a rigid cyclohexane linker are practically useful for the ratiometric measurement of PTPs activity. The design concept described in this paper, using FRET switching by spectral overlap integral and a rigid link that prevents close contact of the two dyes, should also be applicable to other hydrolytic enzymes by introducing other appropriate enzyme-cleavable groups into the fluorescein acceptor. 相似文献
74.
Ahmed Abdel-Lateff 《Tetrahedron letters》2008,49(45):6398-6400
A marine fungal isolate, identified as Chaetomium sp., was cultivated and found to produce a novel benzonaphthyridinedione derivative, chaetominedione (1). In addition to the known fungal metabolites, 2-furancarboxylic acid (2) and 5-(hydroxymethyl)-2-furancarboxylic acid (3) were obtained. The structures of all the compounds were determined based on extensive spectroscopic measurements (1D and 2D NMR, MS, UV, and IR). The total extract and compound 1 had significant inhibitory activity toward p56lck tyrosine kinase (18.7% and 93.6% enzyme inhibition at 200 μg/mL, respectively). 相似文献
75.
In this work, 0.08 mmol L−1 of phthalic acid was introduced as a mobile phase additive to quantify free amino acids (AAs) by hydrophilic interaction liquid chromatography (HILIC) coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS). The addition of phthalic acid significantly increased the signal intensity of protonated AA ions, resulting from the decrease of the relative abundance of AA sodium adducts. Meanwhile, the chromatographic peak shapes of AAs were optimized. As a consequence, there was a noticeable increase in the sensitivity of detection for AAs. The limits of detection (LOD) and quantification (LOQ) of the AAs ranged from 0.0500 to 20.0 ng mL−1 and from 0.100 to 50.0 ng mL−1, respectively, which were 4–50 times lower compared to the values measured without the addition of phthalic acid. The enhanced detection and separation of AAs were obtained by merely adding phthalic acid to the mobile phase without changing other conditions. Eventually, this simple method was validated and successfully applied to the analysis of twenty-four kinds of free AAs in human thyroid carcinoma and para-carcinoma tissues, demonstrating a significant increase of most AAs in thyroid carcinoma tissues (p < 0.05). 相似文献
76.
77.
Dr. Himansu S. Biswal Surjendu Bhattacharyya Prof. Sanjay Wategaonkar 《Chemphyschem》2013,14(18):4165-4176
The present study combines both laser spectroscopy and ab initio calculations to investigate the intermolecular O? H???O hydrogen bonding of complexes of the tyrosine side chain model chromophore compounds phenol (PH) and para‐cresol (pCR) with H2O, MeOH, PH and pCR in the ground (S0) state as well as in the electronic excited (S1) state. All the experimental and computational findings suggest that the H‐bond strength increases in the S1 state and irrespective of the hydrogen bond acceptor used, the dispersion energy contribution to the total interaction energy is about 10–15 % higher in the S1 state compared to that in the S0 state. The alkyl‐substituted (methyl; +I effect) H‐bond acceptor forms a significantly stronger H bond both in the S0 and the S1 state compared to H2O, whereas the aryl‐substituted (phenyl; ?R effect) H‐bond donor shows a minute change in energy compared to H2O. The theoretical study emphasizes the significant role of the dispersive interactions in the case of the pCR and PH dimers, in particular the C? H???O and the C? H???π interactions between the donor and acceptor subunits in controlling the structure and the energetics of the aromatic dimers. The aromatic dimers do not follow the acid–base formalism, which states that the stronger the base, the more red‐shifted is the X? H stretching frequency, and consequently the stronger is the H‐bond strength. This is due to the significant contribution of the dispersion interaction to the total binding energy of these compounds. 相似文献
78.
High quality assays are needed in drug discovery to reduce the high attrition rate of lead compounds during primary screening. Capillary electrophoresis (CE) represents a versatile micro-separation technique for resolution of enzyme-catalyzed reactions, including substrate(s), product(s), cofactor(s) and their stereoisomers, which is needed for reliable characterization of biomolecular interactions in free solution. This review article provides a critical overview of new advances in CE for drug screening over the past five years involving biologically relevant enzymes of therapeutic interest, including transferases, hydrolases, oxidoreductases, and isomerases. The basic principles and major configurations in CE, as well as data processing methods needed for rigorous characterization of enzyme inhibition are described. New developments in functional screening of small molecules that modulate the activity of disease-related enzymes are also discussed. Although inhibition is a widely measured response in most enzyme assays, other important outcomes of ligand interactions on protein structure/function that impact the therapeutic potential of a drug will also be highlighted, such as enzyme stabilization, activation and/or catalytic uncoupling. CE offers a selective platform for drug screening that reduces false-positives while also enabling the analysis of low amounts of complex sample mixtures with minimal sample handling. 相似文献
79.
Carolin Schaab Ralf Christian Kling Jürgen Einsiedel Harald Hübner Tim Clark Dieter Seebach Peter Gmeiner 《ChemistryOpen》2014,3(5):206-218
Subtype-selective agonists of the neurotensin receptor NTS2 represent a promising option for the treatment of neuropathic pain, as NTS2 is involved in the mediation of μ-opioid-independent anti-nociceptive effects. Based on the crystal structure of the subtype NTS1 and previous structure–activity relationships (SARs) indicating a potential role for the sub-pocket around Tyr11 of NT(8–13) in subtype-specific ligand recognition, we have developed new NTS2-selective ligands. Starting from NT(8–13), we replaced the tyrosine unit by β2-amino acids (type 1), by heterocyclic tyrosine bioisosteres (type 2) and peptoid analogues (type 3). We were able to evolve an asymmetric synthesis of a 5-substituted azaindolylalanine and its application as a bioisostere of tyrosine capable of enhancing NTS2 selectivity. The S-configured test compound 2 a, [(S)-3-(pyrazolo[1,5-a]pyridine-5-yl)-propionyl11]NT(8–13), exhibits substantial NTS2 affinity (4.8 nm) and has a nearly 30-fold NTS2 selectivity over NTS1. The (R)-epimer 2 b showed lower NTS2 affinity but more than 600-fold selectivity over NTS1. 相似文献
80.
Chang-Chang Liu Chun Lei Yang Zhong Li-Xin Gao Jing-Ya Li Mei-Hua Yu Jia Li Ai-Jun Hou 《Tetrahedron》2014
Six new grayanane diterpenoids, principinols A–F (1–6), were isolated from Rhododendron principis. Compounds 1 and 2 possess unprecedented 6,10-epoxy and 5α-OH moieties, and 1 and 3 are the first two examples of 9α-H in grayanoids. Their structures were determined by extensive spectroscopic analysis, and the absolute configurations of 1–4 were assigned by single-crystal X-ray crystallography. Compounds 4 and 5 inhibit PTP1B phosphatase activity in vitro. A preliminary structure–activity relationship discussion is presented. 相似文献