全文获取类型
收费全文 | 1049篇 |
免费 | 269篇 |
国内免费 | 8篇 |
专业分类
综合类 | 7篇 |
化学工业 | 982篇 |
金属工艺 | 4篇 |
机械仪表 | 4篇 |
矿业工程 | 1篇 |
能源动力 | 3篇 |
轻工业 | 288篇 |
石油天然气 | 1篇 |
无线电 | 3篇 |
一般工业技术 | 25篇 |
冶金工业 | 1篇 |
原子能技术 | 4篇 |
自动化技术 | 3篇 |
出版年
2024年 | 4篇 |
2023年 | 33篇 |
2022年 | 55篇 |
2021年 | 86篇 |
2020年 | 59篇 |
2019年 | 47篇 |
2018年 | 53篇 |
2017年 | 38篇 |
2016年 | 74篇 |
2015年 | 74篇 |
2014年 | 85篇 |
2013年 | 79篇 |
2012年 | 61篇 |
2011年 | 65篇 |
2010年 | 55篇 |
2009年 | 58篇 |
2008年 | 59篇 |
2007年 | 55篇 |
2006年 | 61篇 |
2005年 | 45篇 |
2004年 | 39篇 |
2003年 | 23篇 |
2002年 | 15篇 |
2001年 | 2篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 8篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 7篇 |
1987年 | 1篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有1326条查询结果,搜索用时 17 毫秒
161.
162.
Reinvestigation confirms action of Δ11-desaturases in spruce budworm moth sex pheromone biosynthesis
The biosynthesis of a large number of sex pheromone components of various moth species has been shown to start with common fatty acids and involve chain shortening by two carbons and introduction of a double bond at the 11–12 position. A recent report indicates that one of these common components, (E)-11-tetradecenyl acetate, is present in the eastern spruce budworm,Choristoneurafumiferana, but is not made by this pathway. Reinvestigation of this insect using in vivo and in vitro techniques indicates that the acetate indeed is made by a sequence of reactions similar to that used in other leafroller moths. In fact, evidence was found for the presence of several 11-desaturase systems in spruce budworm. One produced a large quantity of (Z)-11-hexadecanoic acid, and another produced (E)-11-tetradecanoic acid. It is not known if the small amount of (Z)-11-tetradecanoic acid is produced by either of those two systems or by a third system. A comparison with other species showed that cabbage looper moths have only the first system, redbanded leafroller moths use the last two systems, and European corn borer moths have all three. 相似文献
163.
Richard D. Semba Hu Huang Gerard A. Lutty Jennifer E. Van Eyk Gerald W. Hart 《Proteomics. Clinical applications》2014,8(3-4):218-231
Diabetic retinopathy is a leading cause of blindness worldwide. Despite laser and surgical treatments, antiangiogenic and other therapies, and strict metabolic control, many patients progress to visual impairment and blindness. New insights are needed into the pathophysiology of diabetic retinopathy in order to develop new methods to improve the detection and treatment of disease and the prevention of blindness. Hyperglycemia and diabetes result in increased flux through the hexosamine biosynthetic pathway, which, in turn, results in increased PTM of Ser/Thr residues of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation is involved in regulation of many nuclear and cytoplasmic proteins in a manner similar to protein phosphorylation. Altered O-GlcNAc signaling has been implicated in the pathogenesis of diabetes and may play an important role in the pathogenesis of diabetic retinopathy. The goal of this review is to summarize the biology of the hexosamine biosynthesis pathway and O-GlcNAc signaling, to present the current evidence for the role of O-GlcNAc signaling in diabetes and diabetic retinopathy, and to discuss future directions for research on O-GlcNAc in the pathogenesis of diabetic retinopathy. 相似文献
164.
NAD+‐Dependent Dehydrogenase PctP and Pyridoxal 5′‐Phosphate Dependent Aminotransferase PctC Catalyze the First Postglycosylation Modification of the Sugar Intermediate in Pactamycin Biosynthesis 下载免费PDF全文
Dr. Akane Hirayama Jinmiao Chu Ena Goto Dr. Fumitaka Kudo Prof. Dr. Tadashi Eguchi 《Chembiochem : a European journal of chemical biology》2018,19(2):126-130
The unique five‐membered aminocyclitol core of the antitumor antibiotic pactamycin originates from d ‐glucose, so unprecedented enzymatic modifications of the sugar intermediate are involved in the biosynthesis. However, the order of the modification reactions remains elusive. Herein, we examined the timing of introduction of an amino group into certain sugar‐derived intermediates by using recombinant enzymes that were encoded in the pactamycin biosynthesis gene cluster. We found that the NAD+‐dependent alcohol dehydrogenase PctP and pyridoxal 5′‐phosphate dependent aminotransferase PctC converted N‐acetyl‐d ‐glucosaminyl‐3‐aminoacetophonone into 3′‐amino‐3′‐deoxy‐N‐acetyl‐d ‐glucosaminyl‐3‐aminoacetophenone. Further, N‐acetyl‐d ‐glucosaminyl‐3‐aminophenyl‐β‐oxopropanoic acid ethyl ester was converted into the corresponding 3′‐amino derivative. However, PctP did not oxidize most of the tested d ‐glucose derivatives, including UDP‐GlcNAc. Thus, modification of the GlcNAc moiety in pactamycin biosynthesis appears to occur after the glycosylation of aniline derivatives. 相似文献
165.
Identification of the Biosynthetic Gene Cluster for Himeic Acid A: A Ubiquitin‐Activating Enzyme (E1) Inhibitor in Aspergillus japonicus MF275 下载免费PDF全文
Dr. Makoto Hashimoto Dr. Hikaru Kato Ayako Katsuki Prof. Dr. Sachiko Tsukamoto Prof. Dr. Isao Fujii 《Chembiochem : a European journal of chemical biology》2018,19(6):535-539
Himeic acid A, which is produced by the marine fungus Aspergillus japonicus MF275, is a specific inhibitor of the ubiquitin‐activating enzyme E1 in the ubiquitin–proteasome system. To elucidate the mechanism of himeic acid biosynthesis, feeding experiments with labeled precursors have been performed. The long fatty acyl side chain attached to the pyrone ring is of polyketide origin, whereas the amide substituent is derived from leucine. These results suggest that a polyketide synthase–nonribosomal peptide synthase (PKS‐NRPS) is involved in himeic acid biosynthesis. A candidate gene cluster was selected from the results of genome sequencing analysis. Disruption of the PKS‐NRPS gene by Agrobacterium‐mediated transformation confirms that HimA PKS‐NRPS is involved in himeic acid biosynthesis. Thus, the him biosynthetic gene cluster for himeic acid in A. japonicus MF275 has been identified. 相似文献
166.
Ketonization of Proline Residues in the Peptide Chains of Actinomycins by a 4‐Oxoproline Synthase 下载免费PDF全文
Dr. Siamak Semsary Dr. Ivana Crnovčić Ronja Driller Dr. Joachim Vater Dr. Bernhard Loll Dr. Ullrich Keller 《Chembiochem : a European journal of chemical biology》2018,19(7):706-715
X‐type actinomycins (Acms) contain 4‐hydroxyproline (Acm X0) or 4‐oxoproline (Acm X2) in their β‐pentapeptide lactone rings, whereas their α ring contains proline. We demonstrate that these Acms are formed through asymmetric condensation of Acm half molecules (Acm halves) containing proline with 4‐hydroxyproline‐ or 4‐oxoproline‐containing Acm halves. In turn, we show—using an artificial Acm half analogue (PPL 1) with proline in its peptide chain—their conversion into the 4‐hydroxyproline‐ and 4‐oxoproline‐containing Acm halves, PPL 0 and PPL 2, in mycelial suspensions of Streptomyces antibioticus. Two responsible genes of the Acm X biosynthetic gene cluster of S. antibioticus, saacmM and saacmN, encoding a cytochrome P450 monooxygenase (Cyp) and a ferredoxin were identified. After coexpression in Escherichia coli, their gene products converted PPL 1 into PPL 0 and PPL 2 in vivo as well as in situ in permeabilized cell of the transformed E. coli strain in conjunction with the host‐encoded ferredoxin reductase in a NADH (NADPH)‐dependent manner. saAcmM has high sequence similarity to the Cyp107Z (Ema) family of Cyps, which can convert avermectin B1 into its keto derivative, 4′′‐oxoavermectin B1. Determination of the structure of saAcmM reveals high similarity to the Ema structure but with significant differences in residues decorating their active sites, which defines saAcmM and its orthologues as a distinct new family of peptidylprolineketonizing Cyp. 相似文献
167.
Strictly Conserved Residues in Euphorbia tirucalli β‐Amyrin Cyclase: Trp612 Stabilizes Transient Cation through Cation–π Interaction and CH–π Interaction of Tyr736 with Leu734 Confers Robust Local Protein Architecture 下载免费PDF全文
Yukari Aiba Takumi Watanabe Yuri Terasawa Chiaki Nakano Prof. Dr. Tsutomu Hoshino 《Chembiochem : a European journal of chemical biology》2018,19(5):486-495
The functions of Trp612, Leu734, and Tyr736 of Euphorbia tirucalli β‐amyrin synthase were examined. The aliphatic variants (Ala, Val, Met) of Trp612 showed almost no activity, but the aromatic variants exhibited high activities: 12.5 % of the wild‐type activity for the W612H variant, 43 % for W612F, and 63 % for W612Y. That is, the enzymatic activities of the variants increased in proportion to the increase in π‐electron density. Thus, the major function of Trp612 is to stabilize transient cations through a cation–π interaction. The Phe and Tyr variants caused a distorted folding conformation, especially at the E‐ring site, which generated the aberrantly cyclized products germanicol and lupeol. The L734G and L734A variants exhibited significantly decreased activities but yielded taraxerol in a high production ratio. The Val, Ile, and Met variants showed markedly high activities (56–78 % of wild‐type activity); therefore, appropriate steric bulk is required at this position. The aliphatic variants of Tyr736 showed markedly decreased activities, but the Phe mutant exhibited high activity (67 %), which indicates that the π electrons are critical for catalysis. Homology modeling indicated that Tyr736 and Leu734 are perpendicular to the substrate and are situated face to face, which suggests that a CH–π interaction occurs between Tyr736 and Leu734, reinforcing the protein architecture, and that Tyr736 cannot stabilize cationic intermediates through a cation–π interaction. 相似文献
168.
A Defined and Flexible Pocket Explains Aryl Substrate Promiscuity of the Cahuitamycin Starter Unit–Activating Enzyme CahJ 下载免费PDF全文
Dr. Ashootosh Tripathi Dr. Sung Ryeol Park Dr. Andrew P. Sikkema Dr. Hyo Je Cho Dr. Jianfeng Wu Brian Lee Dr. Chuanwu Xi Prof. Janet L. Smith Prof. David H. Sherman 《Chembiochem : a European journal of chemical biology》2018,19(15):1595-1600
Cahuitamycins are biofilm inhibitors assembled by a convergent nonribosomal peptide synthetase pathway. Previous genetic analysis indicated that a discrete enzyme, CahJ, serves as a gatekeeper for cahuitamycin structural diversification. Here, the CahJ protein was probed structurally and functionally to guide the formation of new analogues by mutasynthetic studies. This analysis enabled the in vivo production of a new cahuitamycin congener through targeted precursor incorporation. 相似文献
169.
170.
Exploiting the Catalytic Diversity of Short‐Chain Dehydrogenases/Reductases: Versatile Enzymes from Plants with Extended Imine Substrate Scope 下载免费PDF全文
Sebastian Roth Dr. Matthew B. Kilgore Prof. Dr. Toni M. Kutchan Prof. Dr. Michael Müller 《Chembiochem : a European journal of chemical biology》2018,19(17):1849-1852
Numerous short‐chain dehydrogenases/reductases (SDRs) have found biocatalytic applications in C=O and C=C (enone) reduction. For NADPH‐dependent C=N reduction, imine reductases (IREDs) have primarily been investigated for extension of the substrate range. Here, we show that SDRs are also suitable for a broad range of imine reductions. The SDR noroxomaritidine reductase (NR) is involved in Amaryllidaceae alkaloid biosynthesis, serving as an enone reductase. We have characterized NR by using a set of typical imine substrates and established that the enzyme is active with all four tested imine compounds (up to 99 % conversion, up to 92 % ee). Remarkably, NR reduced two keto compounds as well, thus highlighting this enzyme family's versatility. Using NR as a template, we have identified an as yet unexplored SDR from the Amaryllidacea Zephyranthes treatiae with imine‐reducing activity (≤95 % ee). Our results encourage the future characterization of SDR family members as a means of discovering new imine‐reducing enzymes. 相似文献