全文获取类型
收费全文 | 1167篇 |
免费 | 151篇 |
国内免费 | 20篇 |
专业分类
化学 | 1175篇 |
晶体学 | 1篇 |
力学 | 4篇 |
综合类 | 10篇 |
数学 | 63篇 |
物理学 | 85篇 |
出版年
2024年 | 1篇 |
2023年 | 19篇 |
2022年 | 61篇 |
2021年 | 75篇 |
2020年 | 72篇 |
2019年 | 41篇 |
2018年 | 46篇 |
2017年 | 42篇 |
2016年 | 52篇 |
2015年 | 60篇 |
2014年 | 69篇 |
2013年 | 58篇 |
2012年 | 81篇 |
2011年 | 74篇 |
2010年 | 67篇 |
2009年 | 61篇 |
2008年 | 42篇 |
2007年 | 64篇 |
2006年 | 57篇 |
2005年 | 47篇 |
2004年 | 78篇 |
2003年 | 21篇 |
2002年 | 27篇 |
2001年 | 20篇 |
2000年 | 14篇 |
1999年 | 9篇 |
1998年 | 9篇 |
1997年 | 12篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 8篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有1338条查询结果,搜索用时 125 毫秒
971.
Fluorimetric determination of aminoglycoside antibiotics using lanthanide probe ion spectroscopy 总被引:9,自引:0,他引:9
The application of probe ion fluorimetry has succeeded in the microdetermination of six aminoglycoside antibiotics: neomycin, streptomycin, gentamicin, tobramycin, amikacin and kanamycin as sulfate salts in pure form and in some pharmaceutical preparations. The method is based on the reaction of Eu3+ ions with aminoglycosides through amino and hydroxy groups. Such interactions enhance the intensity of the 616 nm fluorescence emission of the Eu3+ ion. The fluorescence at 592 nm comes from a non-hypersensitive transition and is not affected by the ligand which is bound to the probe ions. The intensity ratio R, defined as I592/I616 was used to determine the amount of free and bound europium ions. A linear relationship between bound europium ions and aminoglycoside was found within the concentration ranges 20–100 ppm for neomycin, 5–60 ppm for streptomycin, and 10–70 ppm for gentamicin, tobramycin, amikacin, and kanamycin as sulfate salts. The percentage recoveries ranged from 99.22 to 101.07, with standard deviations ranging from ± 1.5 to ± 4.38. The relative stability constants ranged from 5 × 103 to 2 × 104. The optimum reaction conditions were studied and the results obtained compared favourably with the fluorimetric method using fluorescmine reagent. 相似文献
972.
《Analytica chimica acta》2004,520(1-2):57-67
Water- and fat-soluble vitamins were separated on a MetaChem Polaris C18-A (150 mm×4.6 mm, 3 μm particle size) in a single run using combined isocratic and linear gradient elution with a mobile phase consisting of 0.010% trifluoroacetic acid of pH 3.9 (solvent A) and methanol (solvent B) at the flow rate 0.7 ml min−1. A linear gradient profile (A:B) started at 95:5 and was constant in the first 4 min, then linearly decreased up to 2:98 during the next 6 min, then it was constant in the next 20 min and finally linearly increased up to 95:5 ratio of water phase in the last 5 min of the separation. The most suitable detection wavelength for simultaneous vitamin determination was 280 nm. The method was applied for the solid sample of pharmaceutical preparation (B-Komplex), fortified powdered drinks (multi-vitamin) and food samples. The results were in good agreement with the declared values. 相似文献
973.
A simple method for the determination of trace amounts of copper by spectrophotometry is described based on the formation of the copper‐chloro‐(phenyl) glyoxime complex. The molar absorptivities of the complexes at pH 4.0 at 290.5 nm were 0.8 × 104l/mol cm. Optimal conditions such as reagent amounts and pH for the copper determination were reported. The effects of the foreign ions were also investigated. The method was successfully applied for determinations of copper in some natural waters and pharmaceutical samples. 相似文献
974.
《Electroanalysis》2003,15(2):133-138
The preparation of a biosensor based on the enzymatic immobilization in polypyrrole polymer for the detection of antidepressant drugs is described. The enzyme monoamine oxidase (MAO) was immobilized by electropolymerization of pyrrole around a platinum electrode, at a constant potential of +0.75 V (vs. Ag/AgCl) in such a way to obtain a membrane thickness, which was constant and equal to 100 mC/cm2. The biosensor was obtained from a 0.1 M KCl saline solution containing pyrrole at a concentration equal to 0.4 M and 2.5 mU/mL of MAO. The biosensor was adapted to a continuous flow injection analysis system (FIA) with the amperometric detection of hydrogen peroxide produced by enzymatic reaction carried out at a potential of +0.7 V (vs. Ag/AgCl), pH 7.4 and temperature of 37 °C. In optimized flow conditions, the biosensor presented an analytical response for fluoxetine in the interval between 0.67 and 4.33 mM, with a detection limit of 0.10 mM. The analytical use of the biosensor developed was evaluated through analysis of commercial pharmaceutical products containing fluoxetine, available on the Portuguese market. The amperometric flow results obtained do not differ significantly from the values resulting from analysis of the same products by the method proposed by the US Pharmacopeia, with sampling rates of 20–25 samples/hour. 相似文献
975.
976.
Dr. Richard J. D. Hatley Dr. Simon J. F. Macdonald Dr. Robert J. Slack Dr. Joelle Le Dr. Steven B. Ludbrook Dr. Pauline T. Lukey 《Angewandte Chemie (International ed. in English)》2018,57(13):3298-3321
There is a requirement for efficacious and safe medicines to treat diseases with high unmet need. The resurgence in αv‐RGD integrin inhibitor drug discovery is poised to contribute to this requirement. However, drug discovery in the αv integrin space is notoriously difficult due to the receptors being structurally very similar as well as the polar zwitterionic nature of the pharmacophore. This Review aims to guide drug discovery research in this field through an αv inhibitor toolbox, consisting of small molecules and antibodies. Small‐molecule αv tool compounds with extended profiles in αvβ1, 3, 5, 6 and 8 cell adhesion assays, with key physicochemical properties, have been collated to assist in the selection of the right tool for the right experiment. This should also facilitate an understanding of partial selectivity profiles of compounds generated in different assays across research institutions. Prospects for further αv integrin research and the critical importance of target validation are discussed, where increased knowledge of the selectivity for individual RGD αv integrins is key. Insights into the design of small‐molecule RGD chemotypes for topical or oral administration are provided and clinical findings on advanced molecules are examined. 相似文献
977.
Small Molecules Targeting Mycobacterium tuberculosis Type II NADH Dehydrogenase Exhibit Antimycobacterial Activity 下载免费PDF全文
Dr. Michael B. Harbut Dr. Baiyuan Yang Dr. Renhe Liu Dr. Takahiro Yano Dr. Catherine Vilchèze Dr. Bo Cheng Dr. Jonathan Lockner Dr. Hui Guo Dr. Chenguang Yu Prof. Scott G Franzblau Dr. H. Mike Petrassi Prof. William R. Jacobs Jr. Prof. Harvey Rubin Dr. Arnab K. Chatterjee Prof. Feng Wang 《Angewandte Chemie (International ed. in English)》2018,57(13):3478-3482
The generation of ATP through oxidative phosphorylation is an essential metabolic function for Mycobaterium tuberculosis (Mtb), regardless of the growth environment. The type II NADH dehydrogenase (Ndh‐2) is the conduit for electrons into the pathway, and is absent in the mammalian genome, thus making it a potential drug target. Herein, we report the identification of two types of small molecules as selective inhibitors for Ndh‐2 through a multicomponent high‐throughput screen. Both compounds block ATP synthesis, lead to effects consistent with loss of NADH turnover, and importantly, exert bactericidal activity against Mtb. Extensive medicinal chemistry optimization afforded the best analogue with an MIC of 90 nm against Mtb. Moreover, the two scaffolds have differential inhibitory activities against the two homologous Ndh‐2 enzymes in Mtb, which will allow precise control over Ndh‐2 function in Mtb to facilitate the assessment of this anti‐TB drug target. 相似文献
978.
Total Synthesis and Conformational Study of Callyaerin A: Anti‐Tubercular Cyclic Peptide Bearing a Rare Rigidifying (Z)‐2,3‐ Diaminoacrylamide Moiety 下载免费PDF全文
Shengping Zhang Luis M. De Leon Rodriguez Ivanhoe K. H. Leung Gregory M. Cook Paul W. R. Harris Margaret A. Brimble 《Angewandte Chemie (International ed. in English)》2018,57(14):3631-3635
The first synthesis of the anti‐TB cyclic peptide callyaerin A ( 1 ), containing a rare (Z)‐2,3‐diaminoacrylamide bridging motif, is reported. Fmoc‐formylglycine‐diethylacetal was used as a masked equivalent of formylglycine in the synthesis of the linear precursor to 1 . Intramolecular cyclization between the formylglycine residue and the N‐terminal amine in the linear peptide precursor afforded the macrocyclic natural product 1 . Synthetic 1 possessed potent anti‐TB activity (MIC100=32 μm ) while its all‐amide congener was inactive. Variable‐temperature NMR studies of both the natural product and its all‐amide analogue revealed the extraordinary rigidity imposed by this diaminoacrylamide unit on peptide conformation. The work reported herein pinpoints the intrinsic role that the (Z)‐2,3‐diaminoacrylamide moiety confers on peptide bioactivity. 相似文献
979.
Yiyan Yan Xiaohe Xu Xiaokang Jie Jingya Cheng Renren Bai Qi Shuai Yuanyuan Xie 《Tetrahedron letters》2018,59(29):2793-2796
The direct conversion of α,β-unsaturated aldehydes to corresponding nitriles promoted by Pd(OAc)2 and phthalic acid which was hydrolyzed from N-hydroxyphthalimide (NHPI) has been disclosed. Additionally, it was found that when water was used as the solvent, α,β-unsaturated amides was obtained as the main products in good to excellent yields. It was first reported that NHPI was utilized as the nitrogen source to synthesize α,β-unsaturated nitriles and amides from aldehydes. Control experiment demonstrated that aldehydes undergo a process of oximation and dehydration to form nitriles and amides. 相似文献
980.
Jacques Streith 《Comptes Rendus Chimie》2018,21(2):131-151
Home weaving of silk ribbons was introduced in the old canton Basel (Switzerland) during the 16th century. On the basis of the silk threads and natural dyestuffs, it blossomed during the First Industrial Revolution and became the dominant economic activity in that canton. Textile printing on cotton fabric started in 1746 in Mulhouse and the town quickly became a major European textile hub. A first economic turning point occurred in 1865, when artificial dyestuffs were invented and produced in several start-ups, which were subcontractors to the textile industry in the whole “RegioTriRhena” area. After diversification towards polymer, plant protection and pharmaceutical products, the manufacturing of a large spectrum of these products became the principal economic domain during the 20th century. A second economic turning point occurred in the 1970s when the pharmaceutical industry took the lead, thanks to ambitious research and production efforts, and transformed the Basel metropolitan area into the major pharmaceutical hub of continental Europe. Although fundamental research was an old tradition at the University of Basel, applied research, which started in 1854, allowed the Mulhouse Chemistry School to participate effectively in these various scientific domains and accompany both economic turning points. 相似文献