全文获取类型
收费全文 | 439篇 |
免费 | 33篇 |
国内免费 | 7篇 |
专业分类
综合类 | 5篇 |
化学工业 | 203篇 |
金属工艺 | 8篇 |
机械仪表 | 4篇 |
建筑科学 | 5篇 |
能源动力 | 3篇 |
轻工业 | 228篇 |
石油天然气 | 1篇 |
无线电 | 2篇 |
一般工业技术 | 8篇 |
冶金工业 | 2篇 |
原子能技术 | 1篇 |
自动化技术 | 9篇 |
出版年
2024年 | 3篇 |
2023年 | 6篇 |
2022年 | 32篇 |
2021年 | 45篇 |
2020年 | 15篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 15篇 |
2016年 | 11篇 |
2015年 | 25篇 |
2014年 | 25篇 |
2013年 | 23篇 |
2012年 | 30篇 |
2011年 | 42篇 |
2010年 | 17篇 |
2009年 | 38篇 |
2008年 | 16篇 |
2007年 | 21篇 |
2006年 | 17篇 |
2005年 | 12篇 |
2004年 | 8篇 |
2003年 | 5篇 |
2002年 | 10篇 |
2001年 | 3篇 |
2000年 | 7篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 7篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1987年 | 1篇 |
排序方式: 共有479条查询结果,搜索用时 15 毫秒
41.
Douglas Weber David Patsch Annika Neumann Dr. Margit Winkler Prof. Dr. Dörte Rother 《Chembiochem : a European journal of chemical biology》2021,22(10):1823-1832
Accessing aldehydes from carboxylate moieties is often a challenging task. In this regard, carboxylate reductases (CARs) are promising catalysts provided by nature that are able to accomplish this task in just one step, avoiding over-reduction to the alcohol product. However, the heterologous expression of CARs can be quite difficult due to the excessive formation of insoluble protein, thus hindering further characterization and application of the enzyme. Here, the heterologous production of the carboxylate reductase from Nocardia otitidiscaviarum (NoCAR) was optimized by a combination of i) optimized cultivation conditions, ii) post-translational modification with a phosphopantetheinyl transferase and iii) selection of an appropriate expression strain. Especially, the selection of Escherichia coli tuner cells as host had a strong effect on the final 110-fold increase in the specific activity of NoCAR. This highly active NoCAR was used to reduce sodium benzoate to benzaldehyde, and it was successfully assembled with an in vitro regeneration of ATP and NADPH, being capable of reducing about 30 mM sodium benzoate with high selectivity in only 2 h of reaction. 相似文献
42.
Ulrike Vogel Dr. Matthieu Da Costa Carlos Alvarez Quispe Robin Stragier Dr. Henk-Jan Joosten Dr. Koen Beerens Prof. Dr. Tom Desmet 《Chembiochem : a European journal of chemical biology》2023,24(23):e202300549
A promiscuous CDP-tyvelose 2-epimerase (TyvE) from Thermodesulfatator atlanticus (TaTyvE) belonging to the nucleotide sugar active short-chain dehydrogenase/reductase superfamily (NS-SDRs) was recently discovered. TaTyvE performs the slow conversion of NDP-glucose (NDP-Glc) to NDP-mannose (NDP-Man). Here, we present the sequence fingerprints that are indicative of the conversion of UDP-Glc to UDP-Man in TyvE-like enzymes based on the heptagonal box motifs. Our data-mining approach led to the identification of 11 additional TyvE-like enzymes for the conversion of UDP-Glc to UDP-Man. We characterized the top two wild-type candidates, which show a 15- and 20-fold improved catalytic efficiency, respectively, on UDP-Glc compared to TaTyvE. In addition, we present a quadruple variant of one of the identified enzymes with a 70-fold improved catalytic efficiency on UDP-Glc compared to TaTyvE. These findings could help the design of new nucleotide production pathways starting from a cheap sugar substrate like glucose or sucrose. 相似文献
43.
Two anthocyanins (cyanidin-3-O-β-glucoside and peonidin-3-O-β-glucoside) and other phenolic (ferulic acid) were, respectively isolated from black and pigmented brown rices (Oryza sativa L. japonica) and their complete structures were determined by spectroscopic analyses (H NMR, C NMR and MALDI MASS). The HPLC profile of anthocyanins extracted from black rice showed cyanidin-3-O-β-glucoside as the first peak (85%) and peonidin 3-O-β-d-glucoside as the second (15%), while that of pigmented brown rice showed ferulic acid as the first peak (85.7%) and tocols as the second (14.3%). Several tocols were isolated and identified from the unsaponifiable fractions of both rices having some difference on their structures and amounts. The aldose reductase inhibitory activity of isolated compounds was in the following decreasing order: cyanidin-3-glucoside > quercetin > ferulic acid > peonidin-3-glucoside > tocopherol. 相似文献
44.
A Fluorimetric Readout Reporting the Kinetics of Nucleotide‐Induced Human Ribonucleotide Reductase Oligomerization 下载免费PDF全文
Dr. Yuan Fu Dr. Hong‐Yu Lin Somsinee Wisitpitthaya William A. Blessing Prof. Yimon Aye 《Chembiochem : a European journal of chemical biology》2014,15(17):2598-2604
Human ribonucleotide reductase (hRNR) is a target of nucleotide chemotherapeutics in clinical use. The nucleotide‐induced oligomeric regulation of hRNR subunit α is increasingly being recognized as an innate and drug‐relevant mechanism for enzyme activity modulation. In the presence of negative feedback inhibitor dATP and leukemia drug clofarabine nucleotides, hRNR‐α assembles into catalytically inert hexameric complexes, whereas nucleotide effectors that govern substrate specificity typically trigger α‐dimerization. Currently, both knowledge of and tools to interrogate the oligomeric assembly pathway of RNR in any species in real time are lacking. We therefore developed a fluorimetric assay that reliably reports on oligomeric state changes of α with high sensitivity. The oligomerization‐directed fluorescence quenching of hRNR‐α, covalently labeled with two fluorophores, allows for direct readout of hRNR dimeric and hexameric states. We applied the newly developed platform to reveal the timescales of α self‐assembly, driven by the feedback regulator dATP. This information is currently unavailable, despite the pharmaceutical relevance of hRNR oligomeric regulation. 相似文献
45.
Toward the Development of Dual‐Targeted Glyceraldehyde‐3‐phosphate Dehydrogenase/Trypanothione Reductase Inhibitors against Trypanosoma brucei and Trypanosoma cruzi 下载免费PDF全文
Prof. Dr. Federica Belluti Elisa Uliassi Giacomo Veronesi Dr. Christian Bergamini Dr. Marcel Kaiser Prof. Dr. Reto Brun Angelo Viola Prof. Dr. Romana Fato Prof. Dr. Paul A. M. Michels Prof. Dr. R. Luise Krauth‐Siegel Prof. Dr. Andrea Cavalli Prof. Dr. Maria Laura Bolognesi 《ChemMedChem》2014,9(2):371-382
A significant improvement in the treatment of trypanosomiases has been achieved with the recent development of nifurtimox–eflornithine combination therapy (NECT). As an alternative to drug combinations and as a means to overcome most of the antitrypanosomatid drug discovery challenges, a multitarget drug design strategy has been envisaged. To begin testing this hypothesis, we designed and developed a series of quinone–coumarin hybrids against glyceraldehyde‐3‐phosphate dehydrogenase/trypanothione reductase (GAPDH/TR). These enzymes belong to metabolic pathways that are vital to Trypanosoma brucei and Trypanosoma cruzi, and have thus been considered promising drug targets. The synthesized molecules were characterized for their dual‐target antitrypanosomal profile, both in enzyme assays and in in vitro parasite cultures. The merged derivative 2‐{[3‐(3‐dimethylaminopropoxy)‐2‐oxo‐2H‐chromen‐7‐yl]oxy}anthracene‐1,4‐dione ( 10 ) showed an IC50 value of 5.4 μM against TbGAPDH and a concomitant Ki value of 2.32 μM against TcTR. Notably, 2‐{4‐[6‐(2‐dimethylaminoethoxy)‐2‐oxo‐2H‐chromen‐3‐yl]phenoxy}anthracene‐1,4‐dione (compound 6 ) displayed a remarkable EC50 value for T. brucei parasites (0.026 μM ) combined with a very low cytotoxicity toward mammalian L6 cells (7.95 μM ). This promising low toxicity of compound 6 might be at least partially due to the fact that it does not interfere with human glutathione reductase. 相似文献
46.
Feng Li Yongli WangKirk L. Parkin Viriya NitteranonJin Liang Wenjian YangYing Li Guodong ZhangQiuhui Hu 《Food research international (Ottawa, Ont.)》2011,44(6):1597-1603
To investigate the potential activity of ginger rhizome extracts to induce quinone reductase (QR), we performed bioactivity-guided fractionation using a murine hepatoma cell (Hepa 1c1c7) bioassay. Anti-inflammatory effects were then studied utilizing lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW 264.7) cells. An ethyl acetate-partitioned fraction from ethanolic extract, rich in both QR inducing potency and anti-inflammatory activity, was subjected to repeated silica gel column and preparative thin layer chromatography to yield three compounds. The three isolated compounds were [6]-shogaol, 1-dehydro-[6]-gingerdione and hexahydrocurcumin. [6]-Dehydroshogaol, a minor component in ginger rhizome, was chemically synthesized and used for comparison in the subsequent bioassay based on its excellent QR inducing potency. Results showed that [6]-dehydroshogaol had the highest ability to induce QR activity (CD = 9.23 ± 0.22 ??M), followed by 1-dehydro-[6]-gingerdione (CD = 13.24 ± 0.45 ??M), and then hexahydrocurcumin (CD = 68.81 ± 3.90 ??M). Increasing QR activity in induced cells was associated with elevated expression of NQO-1 protein as confirmed by Western blot. [6]-Dehydroshogaol, [6]-shogaol and 1-dehydro-[6]-gingerdione were also potent inhibitors of nitric oxide (NO) synthesis in activated macrophages. Their IC50 values ranged from 5.80 ± 1.27 to 25.06 ± 4.86 ??M. Hexahydrocurcumin exhibited the weakest inhibitory effect (IC50 = 304.76 ± 54.80 ??M). These findings contribute to our theoretical understanding of the potential beneficial effects of consuming ginger as food and/or dietary supplement. 相似文献
47.
Several different organic materials, typical of those used in passive treatment systems for mine influenced water, were tested for their ability to support sulfate-reducing bacteria and sulfate reduction in an anaerobic biological reactor (ABR). The quantity of sulfate-reducing bacteria (SRB) in each organic material, as determined using quantitative polymerase chain reaction (q-PCR) of the dissimilatory sulfite reductase (dsr) gene, correlated with the initial C/N ratio of each material. Potential sulfate reduction rates measured in the laboratory ranked silage > compost = molasses/hay > cattails > pulp mill biosolids and correlated with the q-PCR estimates of SRB in the submerged materials. A comparison of bacterial communities using 16S rRNA gene clone library sequencing revealed similar distribution of clones among the phyla Bacteroidetes, Firmicutes and Proteobacteria for silage, compost and molasses/hay after 174 days of exposure in the seepage water. Silage, the most successful material tested, contained more δ-Proteobacteria-related sequences than the other materials and Spirochaetes-related clones were more abundant in silage than in compost or molasses/hay. According to sequenced dsr clones, the SRB community in silage differed from that for compost and molasses/hay, with fewer Desulfovibrio- and more Desulfomicrobium-related sequences in the silage. Pulp mill biosolids used in the ABR since 2004 contained an overall bacterial community that was more diverse than those for the freshly submerged organics, but only Desulfovibrio desulfuricans-related sequences were found in the dsr library. 相似文献
48.
以菠菜为实验材料,研究低温贮藏条件下(4℃)密闭气体环境对菠菜贮藏品质,尤其对硝酸盐、亚硝酸盐及硝酸还原酶等酶活性的影响。结果表明:与对照(非密闭环境)相比,低温密闭气体环境可显著减缓菠菜可溶性固形物、VC、叶绿素等贮藏品质的下降,维持菠菜较高的硝酸还原酶(NR)活性和抗逆酶活性(SOD、POD、CAT),抑制丙二醛的产生,贮藏8d硝酸盐和亚硝酸盐分别为1318.44、0.42mg/kg,较对照分别降低了31.96%、26.19%,实验表明低温密闭气体环境有效降低了硝酸盐和亚硝酸盐的累积,提升了菠菜的安全贮运品质。 相似文献
49.
Alonzo Gonzlez-Gonzlez Oscar Snchez-Snchez R. Luise Krauth-Siegel Maria Laura Bolognesi Rogelio Gmez-Escobedo Benjamín Nogueda-Torres Lenci K. Vzquez-Jimnez Emma Saavedra Rusely Encalada Jos Carlos Espinoza-Hicks Alma D. Paz-Gonzlez Gildardo Rivera 《International journal of molecular sciences》2022,23(21)
American trypanosomiasis is a worldwide health problem that requires attention due to ineffective treatment options. We evaluated n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives against trypomastigotes of the Trypanosoma cruzi strains NINOA and INC-5. An in silico analysis of the interactions of 1,4-di-N-oxide on the active site of trypanothione reductase (TR) and an enzyme inhibition study was carried out. The n-butyl series compound identified as T-150 had the best trypanocidal activity against T. cruzi trypomastigotes, with a 13% TR inhibition at 44 μM. The derivative T-147 behaved as a mixed inhibitor with Ki and Ki’ inhibition constants of 11.4 and 60.8 µM, respectively. This finding is comparable to the TR inhibitor mepacrine (Ki = 19 µM). 相似文献
50.
Paul R. J. Ames Alessia Arcaro Matilde Caruso Maria Graf Vincenzo Marottoli Fabrizio Gentile 《International journal of molecular sciences》2022,23(23)
We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (p = 0.001) with wide heterogeneity (I2 = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles n = 1, USA n = 5) yielded a neutral effect size, four (India n = 1, Arab countries n = 3) favoured SCD (p < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, p = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, p = 0.47); removal of one paediatric study yielded a significant effect size (p = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS. 相似文献