全文获取类型
收费全文 | 237篇 |
免费 | 25篇 |
国内免费 | 5篇 |
专业分类
电工技术 | 1篇 |
综合类 | 5篇 |
化学工业 | 131篇 |
金属工艺 | 3篇 |
机械仪表 | 1篇 |
建筑科学 | 1篇 |
轻工业 | 113篇 |
石油天然气 | 3篇 |
无线电 | 2篇 |
一般工业技术 | 1篇 |
冶金工业 | 1篇 |
原子能技术 | 5篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2022年 | 28篇 |
2021年 | 19篇 |
2020年 | 18篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 14篇 |
2014年 | 20篇 |
2013年 | 14篇 |
2012年 | 14篇 |
2011年 | 16篇 |
2010年 | 6篇 |
2009年 | 9篇 |
2008年 | 13篇 |
2007年 | 6篇 |
2006年 | 10篇 |
2005年 | 6篇 |
2004年 | 7篇 |
2003年 | 7篇 |
2002年 | 7篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有267条查询结果,搜索用时 15 毫秒
21.
Yamamoto T Mukai K Yamashita H Kubota M Fukuda S Kurimoto M Tsujisaka Y 《Journal of Bioscience and Bioengineering》2005,100(2):212-215
Random mutation by error-prone PCR was introduced into kojibiose phosphorylase from Thermoanaerobacter brockii ATCC35047. One thermostable mutant enzyme, D513N, was isolated. The D513N mutant enzyme showed an optimum temperature of 67.5-70 degrees C (the wild type, 65 degrees C), and thermostability up to 67.5 degrees C (the wild type, up to 60 degrees C). The half-lives of D513N were estimated to be 135 h at 60 degrees C, 110 min at 70 degrees C and 6 min at 75 degrees C, respectively. They were about 1.6-fold, 7-fold and 6-fold longer than those of the wild-type enzyme, respectively. 相似文献
22.
23.
Anastasia Parchina Prof. Dr. Matheus Froeyen Lia Margamuljana Prof. Dr. Jef Rozenski Dr. Steven De Jonghe Dr. Yves Briers Prof. Dr. Rob Lavigne Prof. Dr. Piet Herdewijn Prof. Dr. Eveline Lescrinier 《ChemMedChem》2013,8(8):1373-1383
The urgent need for new antibiotics poses a challenge to target un(der)exploited vital cellular processes. Thymidylate biosynthesis is one such process due to its crucial role in DNA replication and repair. Thymidylate synthases (TS) catalyze a crucial step in the biosynthesis of thymidine 5‐triphosphate (TTP), an elementary building block required for DNA synthesis and repair. To date, TS inhibitors have only been successfully applied in anticancer therapy due to their lack of specificity for antimicrobial versus human enzymes. However, the discovery of a new family of TS enzymes (ThyX) in a range of pathogenic bacteria that is structurally and biochemically different from the “classic” TS (ThyA) has opened the possibility to develop selective ThyX inhibitors as potent antimicrobial drugs. Here, the interaction of the known inhibitor 5‐(3‐octanamidoprop‐1yn‐1yl)‐2′‐deoxyuridine‐5′‐monophosphate ( 1 ) with Mycobacterium tuberculosis ThyX enzyme is explored using molecular modeling starting from published crystal structures, with further confirmation through NMR experiments. While the deoxyuridylate (dUMP) moiety of compound 1 occupies the cavity of the natural substrate in ThyX, the rest of the ligand (the “5‐alkynyl tail”) extends to the outside of the enzyme between two of its four subunits. The hydrophobic pocket that accommodates the alkyl part of the tail is formed by displacement of Tyr 44.C, Tyr 108.A and Lys 165.A. Changes to the resonance of the Lys 165 NH3 group upon ligand binding were monitored in a titration experiment by 2D HISQC NMR. Guided by the results of the modeling and NMR studies, and inspired by the success of acyclic antiviral nucleosides, compounds where a 5‐alkynyl uracyl moiety is coupled to an acyclic nucleoside phosphonate (ANP) were synthesized and evaluated. Of the compounds evaluated, sodium (6‐(5‐(3‐octanamidoprop‐1‐yn‐1‐yl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)hexyl)phosphonate ( 3 e ) exhibited 43 % of inhibitory effect on ThyX at 50 μM . While only modest activity was achieved, this is the first example of an ANP inhibiting ThyX, and these results can be used to further guide structural modifications to this class to develop more potent compounds with potential application as antibacterial agents acting through a novel mechanism of action. 相似文献
24.
Ryszard T. Smolenski Magdi H. Yacoub Anne-Marie L. Seymour 《Magma (New York, N.Y.)》1994,2(3):417-420
Ischemia can cause release of adenosine and purine catabolites from the heart, through the breakdown of ATP. If repeated periods of ischemia are induced, the efflux of purines is markedly reduced, although it is not clear if this is beneficial for the long-term survival of the heart. We have investigated changes in high-energy phosphates and purine release in the isolated perfused rat heart using31P NMR spectroscopy and high-performance liquid chromatography. Hearts were subjected to one of the following protocols: Group A—1 min of total global ischemia (TGI) after 40 min, 60 min, and 85 min of perfusion (a total of 3 × 1 min ischemia); Group B—1 min of TGI after 40 min of perfusion, 10 min of TGI after 50 min of perfusion, and a final 1 min of TGI after 85 min of perfusion. The profile of high-energy phosphate metabolites, Pi accumulation and purine release was similar for each 1-min period of TGI in Group A, whereas phosphocreatine content was increased and ATP content reduced by an extended period of TGI in Group B, leading to a less severe acidosis and purine efflux in the final 1 min of TGI at 85 min of perfusion. In conclusion, the reduced purine release observed in Group B may be related to the preischemic ATP pool size and accessibility and the increased myocardial energy reserve in the form of phosphocreatine. 相似文献
25.
Synthesis,Photophysical Properties and Incorporation of a Highly Emissive and Environment‐Sensitive Uridine Analogue Based on the Lucifer Chromophore
下载免费PDF全文
![点击此处可从《Chembiochem : a European journal of chemical biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Arun A. Tanpure Dr. Seergazhi G. Srivatsan 《Chembiochem : a European journal of chemical biology》2014,15(9):1309-1316
The majority of fluorescent nucleoside analogues used in nucleic acid studies have excitation maxima in the UV region and show very low fluorescence within oligonucleotides (ONs); hence, they cannot be utilised with certain fluorescence methods and for cell‐based analysis. Here, we describe the synthesis, photophysical properties and incorporation of a highly emissive and environment‐sensitive uridine analogue, derived by attaching a Lucifer chromophore (1,8‐naphthalimide core) at the 5‐position of uracil. The emissive nucleoside displays excitation and emission maxima in the visible region and exhibits high quantum yield. Importantly, when incorporated into ON duplexes it retains appreciable fluorescence efficiency and is sensitive to the neighbouring base environment. Notably, the nucleoside signals the presence of purine repeats in ON duplexes with an enhancement in fluorescence intensity, a property rarely displayed by other nucleoside analogues. 相似文献
26.
27.
The DiPPro Approach: Synthesis,Hydrolysis, and Antiviral Activity of Lipophilic d4T Diphosphate Prodrugs
下载免费PDF全文
![点击此处可从《ChemMedChem》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Bioreversible protection of the β‐phosphate group of nucleoside diphosphates (NDPs) as bis(acyloxybenzyl)phosphate esters is presented. To investigate the structure–activity relationship of these potential NDP prodrugs (DiPPro drugs) a series of DiPPro compounds was synthesized bearing fatty acids of various lengths and d4T as a model nucleoside. For synthesis of the lipophilically modified diphosphate group, preformed phosphoramidites were allowed to react with nucleotides, and the β‐PIII moiety was subsequently oxidized. The chemical and enzymatic stability of these prodrugs was studied in different media such as phosphate buffer (pH 7.3) or CEM cell extracts. In all media, the hydrolysis rate was clearly dependent on the acyl moiety and decreased with increasing alkyl chain length. The compounds showed a markedly lower half‐life in cell extracts than in pH 7.3 phosphate buffer due to the presence of enzyme‐catalyzed cleavage. In all media, the DiPPro compounds released d4T diphosphate (d4TDP) as the main product beside d4TMP. In antiviral assays, the compounds proved to be at least as potent as d4T against HIV‐1 and 2 in wild‐type CEM/0 cells. As a proof of concept, compounds with longer acyl residues showed very good anti‐HIV activities in thymidine‐kinase‐deficient cells (CEM/TK?), indicating their ability to penetrate cell membranes and the delivery of phosphorylated metabolites. 相似文献
28.
Nucleoside Triphosphates as Promoters to Enhance Nanoceria Enzyme‐like Activity and for Single‐Nucleotide Polymorphism Typing
下载免费PDF全文
![点击此处可从《Advanced functional materials》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nucleoside triphosphates (NTPs) can improve the oxidase‐like activity of nanoceria and the enhancement is correlated with the type of NTP. This effect is demonstrated to be as a result of the coupling of the oxidative reaction with the NTP hydrolysis reactions, as the nanoceria has both oxidase‐like and phosphatase‐like activities. The differences reflect the different dephosphorylation catalytic activities of nanoceria to the NTP used. Furthermore, based on the NTP‐promoted oxidase‐like activity of nanoceria and the differences among the different types of NTPs, series effective and high‐throughput colorimetric assays for single‐nucleotide polymorphism (SNP) typing are developed. 相似文献
29.
Marc De Doncker Chloé De Graeve Dr. Jorick Franceus Dr. Koen Beerens Prof. Vladimír Křen Dr. Helena Pelantová Dr. Ronny Vercauteren Prof. Dr. Tom Desmet 《Chembiochem : a European journal of chemical biology》2021,22(23):3319-3325
The substantial increase in DNA sequencing efforts has led to a rapid expansion of available sequences in glycoside hydrolase families. The ever-increasing sequence space presents considerable opportunities for the search for enzymes with novel functionalities. In this work, the sequence-function space of glycoside hydrolase family 94 (GH94) was explored in detail, using a combined approach of phylogenetic analysis and sequence similarity networks. The identification and experimental screening of unknown clusters led to the discovery of an enzyme from the soil bacterium Paenibacillus polymyxa that acts as a 4-O-β-d -glucosyl-d -galactose phosphorylase (GGalP), a specificity that has not been reported to date. Detailed characterization of GGalP revealed that its kinetic parameters were consistent with those of other known phosphorylases. Furthermore, the enzyme could be used for production of the rare disaccharides 4-O-β-d -glucosyl-d -galactose and 4-O-β-d -glucosyl-l -arabinose. Our current work highlights the power of rational sequence space exploration in the search for novel enzyme specificities, as well as the potential of phosphorylases for rare disaccharide synthesis. 相似文献
30.