全文获取类型
收费全文 | 1042篇 |
免费 | 115篇 |
国内免费 | 98篇 |
专业分类
化学 | 1231篇 |
晶体学 | 1篇 |
力学 | 1篇 |
综合类 | 7篇 |
数学 | 1篇 |
物理学 | 14篇 |
出版年
2024年 | 1篇 |
2023年 | 7篇 |
2022年 | 38篇 |
2021年 | 41篇 |
2020年 | 55篇 |
2019年 | 41篇 |
2018年 | 29篇 |
2017年 | 25篇 |
2016年 | 45篇 |
2015年 | 45篇 |
2014年 | 44篇 |
2013年 | 63篇 |
2012年 | 59篇 |
2011年 | 39篇 |
2010年 | 54篇 |
2009年 | 55篇 |
2008年 | 54篇 |
2007年 | 53篇 |
2006年 | 58篇 |
2005年 | 41篇 |
2004年 | 51篇 |
2003年 | 53篇 |
2002年 | 103篇 |
2001年 | 24篇 |
2000年 | 17篇 |
1999年 | 19篇 |
1998年 | 18篇 |
1997年 | 14篇 |
1996年 | 14篇 |
1995年 | 17篇 |
1994年 | 16篇 |
1993年 | 14篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有1255条查询结果,搜索用时 15 毫秒
171.
Bauer-Siebenlist B Dechert S Meyer F 《Chemistry (Weinheim an der Bergstrasse, Germany)》2005,11(18):5343-5352
A series of highly preorganized pyrazolate-based dinuclear zinc complexes has been studied as functional synthetic analogues of metallo-beta-lactamases, a class of bacterial enzymes that cause serious clinical problems because of their degradation of common beta-lactam antibiotics. We have investigated the hydrolytic cleavage of penicillin G mediated by the different dinuclear zinc complexes, and have deduced structure-activity correlations. While cooperative effects of the adjacent metal ions might be operative, these are found to either enhance or diminish beta-lactamase activity with respect to a single free zinc. Drastic differences in activity are ascribed to a lack of accessible binding sites after incorporation of the substrate within the bimetallic pocket of 2 and 4, whereas partial detachment of hemilabile ligand side arms in 1 and 3 opens up available coordination sites for nucleophile activation and/or for binding and polarisation of the beta-lactam amide oxygen atom. This interpretation has been corroborated by NMR spectroscopic and mass spectrometric evidence as well as by X-ray crystallography of several adducts formed between the pyrazolate-based dinuclear zinc scaffolds and the small substrate analogue oxazetidinylacetate (oaa), 5-7. In all adducts, the carboxylate group of oaa is the primary anchoring site and is nested in a bridging position within the bimetallic pocket. However, zinc binding of the beta-lactam amide oxygen atom has been confirmed crystallographically for the first time in 7, in which additional open-site coordination sites are available. 相似文献
172.
173.
174.
175.
176.
von Nussbaum F Brands M Hinzen B Weigand S Häbich D 《Angewandte Chemie (International ed. in English)》2006,45(31):5072-5129
To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti-infectives. Surprisingly, numerous "old" classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the "old fashioned" natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target-finding tools from biology (reversed genomics) is one option for their revival. 相似文献
177.
178.
179.
This review covers the main aspects concerning the chemistry, the biological activity and the analytical determination of oxazolidinones, the only new class of synthetic antibiotics advanced in clinical use over the past 50 years. They are characterized by a chemical structure including the oxazolidone ring with the S configuration of substituent at C5, the acylaminomethyl group linked to C5 and the N-aryl substituent. The synthesis of oxazolidinones has gained increasing interest due to their unique mechanism of action that assures high antibiotic efficiency and low susceptibility to resistance mechanisms. Here, the main features of oxazolidinone antibiotics licensed or under development, such as Linezolid, Sutezolid, Eperezolid, Radezolid, Contezolid, Posizolid, Tedizolid, Delpazolid and TBI-223, are discussed. As they are protein synthesis inhibitors active against a wide spectrum of multidrug-resistant Gram-positive bacteria, their biological activity is carefully analyzed, together with the drug delivery systems recently developed to overcome the poor oxazolidinone water solubility. Finally, the most employed analytical techniques for oxazolidinone determination in different matrices, such as biological fluids, tissues, drugs and natural waters, are reviewed. Most are based on HPLC (High Performance Liquid Chromatography) coupled with UV-Vis or mass spectrometer detectors, but, to a lesser extent are also based on spectrofluorimetry or voltammetry. 相似文献
180.
Meghdad Pirsaheb Hiva Hosseini Hasan Mohamadi Sorkali Negar Noori 《International journal of environmental analytical chemistry》2019,99(2):112-123
In the present study, a new method for extraction and preconcentration of amoxicillin and ceftriaxone was used in hospitalised sewage samples, called vortex-assisted liquid-phase microextraction based on the solidification of deep eutectic solvent. Samples were analysed by high-performance liquid chromatography–ultraviolet detection after preparation and extraction. In this method, the new deep eutectic solvent is used as the extraction solvent, which is obtained from the combination of 1-decyl-3-methylimidazolium chloride and n-butanoic acid. The important advantages of this novel extraction solvent include material stability, low density and good freezing point near room temperature. Under the optimum conditions, enrichment factors are in the range of 164–172. Repeatability and reproducibility of the method based on seven replicate measurements of 50.0 µg L?1 of the target analytes in analysed samples were in the range of 2.1–3.5% and 3.8–5.2%, respectively. The limit of detections and linearity are in the range of 0.005–0.10 and 3–600 µg L?1, respectively. The method was successfully applied for the determination of amoxicillin and ceftriaxone in the real sewage samples. The relative recoveries of sewage samples spiked with amoxicillin and ceftriaxone are 91–107%. 相似文献