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81.
Erik Böer Anja Schröter Rüdiger Bode Michael Piontek Gotthard Kunze 《Yeast (Chichester, England)》2009,26(2):83-93
In Arxula adeninivorans nitrate assimilation is mediated by the combined actions of a nitrate transporter, a nitrate reductase and a nitrite reductase. Single‐copy genes for these activities (AYNT1, AYNR1, AYNI1, respectively) form a 9103 bp gene cluster localized on chromosome 2. The 3210 bp AYNI1 ORF codes for a protein of 1070 amino acids, which exhibits a high degree of identity to nitrite reductases from the yeasts Pichia anomala (58%), Hansenula polymorpha (58%) and Dekkera bruxellensis (54%). The second ORF (AYNR1, 2535 bp) encodes a nitrate reductase of 845 residues that shows significant (51%) identity to nitrate reductases of P. anomala and H. polymorpha. The third ORF in the cluster (AYNT1, 1518 bp) specifies a nitrate transporter with 506 amino acids, which is 46% identical to that of H. polymorpha. The three genes are independently expressed upon induction with NaNO3. We quantitatively analysed the promoter activities by qRT–PCR and after fusing individual promoter fragments to the phytase (phyK) gene from Klebsiella sp. ASR1. The AYNI1 promoter was found to exhibit the highest activity, followed by the AYNT1 and AYNR1 elements. Direct measurements of nitrate and nitrite reductase activities performed after induction with NaNO3 are compatible with these results. Both enzymes show optimal activity at around 42°C and near‐neutral pH, and require FAD as a co‐factor and NADPH as electron donor. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
82.
A role for mevalonate in cancer development has long been suggested by findings that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity is elevated in malignant cells. Increased synthesis mevalonate and mevalonate-derived nonsterol isoprenoids supports increased cell proliferation through the activation of growth-regulatory proteins and oncoproteins, and by promoting DNA synthesis. We have recently shown that mevalonate promotes the growth of human breast cancer cells both in culture and as tumors grown in nude mice. Inhibition mevalonate synthesis, therefore, may be an effective strategy to impair the growth of malignant breast cells. Several dietary compounds with known anti-cancer effects are also reported to inhibit HMG-CoA reductase activity. Here, we review evidence suggesting that inhibition of mevalonate synthesis may mediate the protective effects of cholesterol, plant isoprenoids, genistein, and long-chain n-3 polyunsaturated fatty acids (PUFAs) on experimental breast cancer. 相似文献
83.
拟热带假丝酵母中羰基还原酶的纯化及其酶学性质研究 总被引:2,自引:1,他引:1
从拟热带假丝酵母Candida pseudotropicalis 104(C104)中,通过离子交换层析和蓝色琼脂糖亲和层析分离得到依赖于辅酶NAD(H)的羰基还原酶,酶的分子量约为37.5 kD.催化氧化反应的最适pH为8.5,催化还原反应的最适DH为6.0~6.5,最适反应温度均为50℃.该酶热稳定性较低,在pH7.0~8.5环境下较稳定,多数重金属离子均能导致酶活力下降.该酶的反应底物广泛,能高选择性催化还原多种氯代苯乙酮衍生物,其中还原苯乙酮、2'-氯-苯乙酮、3'-氯-苯乙酮和4'-氯-苯乙酮可产生对应的s型醇,其对映体过剩值(e.e.)均达到将近100%.底物上取代基团的位阻效应和电荷诱导效应是羰基还原酶还原底物活力大小的重要影响因素. 相似文献
84.
Laura E. Pedró Rosa D. Rajasekhar Reddy Dr. Sherry F. Queener Prof. Lawrence W. Miller Prof. 《Chembiochem : a European journal of chemical biology》2009,10(9):1462-1464
Antifolate labels : Molecules that bind specifically and with high affinity to proteins can be developed into powerful tools for chemical biology. The interaction between substituted 5‐benzyl pyrimidines and dihydrofolate reductase can be exploited for chemically labeling fusion proteins in mammalian cells.
85.
Christian Eberle Johannes A. Burkhard Bernhard Stump Marcel Kaiser Reto Brun Prof. Dr. R. Luise Krauth‐Siegel Prof. Dr. François Diederich Prof. Dr. 《ChemMedChem》2009,4(12):2034-2044
Trypanothione reductase (TR) is a flavoenzyme unique to trypanosomatid parasites and a target for lead discovery programs. Various inhibitor scaffolds have emerged in the past, exhibiting moderate affinity for the parasite enzyme. Herein we show that the combination of two structural motifs of known TR inhibitors — diaryl sulfides and mepacrine — enables the simultaneous addressing of two hydrophobic patches in the active site. The binding efficacy of these conjugates is enhanced over that of the respective parent inhibitors. They show Kic values for the parasite enzyme down to 0.9±0.1 μm and exhibit high selectivity for TR over human glutathione reductase (GR). Despite their considerable molecular mass and in some cases permanent positive charges, in vitro studies revealed IC50 values in the low micromolar to sub‐micromolar range against Trypanosoma brucei rhodesiense and Trypanosoma cruzi, as well as the malaria parasite Plasmodium falciparum, which lack trypanothione metabolism. The inhibitors exhibit strong fluorescence due to their aminoacridine moiety. This feature allows visualization of the drugs in the parasite where high accumulation was observed by fluorescence microscopy even after short exposure times. 相似文献
86.
Stephen Patterson Dr. Deuan C. Jones Dr. Emma J. Shanks Dr. Julie A. Frearson Prof. Ian H. Gilbert Prof. Paul G. Wyatt Prof. Alan H. Fairlamb Prof. 《ChemMedChem》2009,4(8):1341-1353
Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP ( 1 , 1‐(1‐benzo[b]thiophen‐2‐yl‐cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (Ki=1 μM ) and biologically active against bloodstream T. brucei (EC50=10 μM ), but with poor selectivity against mammalian MRC5 cells (EC50=29 μM ). Analogues with improved enzymatic and biological activity were obtained. The structure–activity relationships of this novel series are discussed. 相似文献
87.
John L. Richardson Dr. Isabelle R. E. Nett Dr. Deuan C. Jones Dr. Mohamed H. Abdille Ian H. Gilbert Prof. Alan H. Fairlamb Prof. 《ChemMedChem》2009,4(8):1333-1340
Trypanothione reductase (TryR) is a key validated enzyme in the trypanothione‐based redox metabolism of pathogenic trypanosomes and leishmania parasites. This system is absent in humans, being replaced with glutathione and glutathione reductase, and as such offers a target for selective inhibition. As part of a program to discover antiparasitic drugs, the LOPAC1280 library of 1266 compounds was screened against TryR and the top hits evaluated against glutathione reductase and T. brucei parasites. The top hits included a number of known tricyclic neuroleptic drugs along with other new scaffolds for TryR. Three novel druglike hits were identified and SAR studies on one of these using information from the tricyclic neuroleptic agents led to the discovery of a competitive inhibitor (Ki=330 nM ) with an improved potency against T. brucei (EC50=775 nM ). 相似文献
88.
89.
Different amino acid derivatives were synthesized during cultivation of a Monascus species. Derivatives exhibiting an inhibitory activity against HMG-CoA reductase were screened by in vitro tests. The threonine derivative had a high inhibitory activity of 38% while four other derivatives showed a greater than 23% activity. The orange monascus pigment showed a high activity of 36%. In vivo tests using female C57BL/6 mice were performed with the threonine derivative and orange pigment. Changes in the cholesterol and lipid levels in mice due to addition of the pigments were investigated. The total cholesterol (TC) level of mouse serum was reduced by 8–9% with the threonine derivative and by 16% with orange pigment. Supplementation with the threonine derivative and orange pigment decreased the LDL cholesterol level by 18–26% and increased the HDL cholesterol level by 1–9%. The atherogenic index (AI) value was reduced by 23–27% with pigment supplementation. The anti-atherosclerosis effect of monascus pigments can be induced by control of the lipid content in the serum rather than in the liver of mice. 相似文献
90.
目的研究玉米醇溶蛋白与D-木糖在65%(V:V)乙醇溶液中的美拉德反应及所得美拉德反应产物在反溶剂沉淀法制备姜黄素纳米颗粒中的应用。方法将玉米醇溶蛋白与D-木糖在乙醇溶中加热,利用所得产物通过反溶剂沉淀法制备姜黄素纳米颗粒,并对纳米颗粒进行表征。结果当D-木糖与玉米醇溶蛋白混合质量比为2:1、反应体系pH值为13.0、反应温度为90℃、反应时间为90 min时,反应体系的A290和A420值最大。利用在该条件下得到的美拉德反应产物通过反溶剂法制备姜黄素纳米颗粒,与未经修饰的玉米醇溶蛋白按照相同方法制备的姜黄素纳米颗粒相比,前者在水中的分散性明显提高,包埋效率和载药量分别显著增加113%和56%,且具有更好的缓释性能和贮藏稳定性。结论美拉德反应修饰的玉米醇溶蛋白在反溶剂沉淀法纳米颗粒的制备中具有广阔的应用前景。 相似文献