全文获取类型
收费全文 | 876篇 |
免费 | 109篇 |
国内免费 | 39篇 |
专业分类
化学 | 1006篇 |
综合类 | 8篇 |
物理学 | 10篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 40篇 |
2021年 | 40篇 |
2020年 | 53篇 |
2019年 | 38篇 |
2018年 | 25篇 |
2017年 | 23篇 |
2016年 | 45篇 |
2015年 | 41篇 |
2014年 | 38篇 |
2013年 | 52篇 |
2012年 | 55篇 |
2011年 | 34篇 |
2010年 | 43篇 |
2009年 | 49篇 |
2008年 | 46篇 |
2007年 | 50篇 |
2006年 | 44篇 |
2005年 | 38篇 |
2004年 | 36篇 |
2003年 | 46篇 |
2002年 | 97篇 |
2001年 | 13篇 |
2000年 | 4篇 |
1999年 | 12篇 |
1998年 | 6篇 |
1997年 | 10篇 |
1996年 | 5篇 |
1995年 | 10篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
排序方式: 共有1024条查询结果,搜索用时 15 毫秒
91.
Aminoglycoside microarrays to explore interactions of antibiotics with RNAs and proteins 总被引:3,自引:0,他引:3
RNA is an important target for drug discovery efforts. Several clinically used aminoglycoside antibiotics bind to bacterial rRNA and inhibit protein synthesis. Aminoglycosides, however, are losing efficacy due to their inherent toxicity and the increase in antibiotic resistance. Targeting of other RNAs is also becoming more attractive thanks to the discovery of new potential RNA drug targets through genome sequencing and biochemical efforts. Identification of new compounds that target RNA is therefore urgent, and we report here on the development of rapid screening methods to probe binding of low molecular weight ligands to proteins and RNAs. A series of aminoglycosides has been immobilized onto glass microscope slides, and binding to proteins and RNAs has been detected by fluorescence. Construction and analysis of the arrays is completed by standard DNA genechip technology. Binding of immobilized aminoglycosides to proteins that are models for study of aminoglycoside toxicity (DNA polymerase and phospholipase C), small RNA oligonucleotide mimics of aminoglycoside binding sites in the ribosome (rRNA A-site mimics), and a large (approximately 400 nucleotide) group I ribozyme RNA is detected. The ability to screen large RNAs alleviates many complications associated with binding experiments that use isolated truncated regions from larger RNAs. These studies lay the foundation for rapid identification of small organic ligands from combinatorial libraries that exhibit strong and selective RNA binding while displaying decreased affinity to toxicity-causing proteins. 相似文献
92.
Antibiotics are precious resources in the fight to combat bacterial infections caused by pathogenic organisms. Vancomycin is one of the antibiotics of last resort in the treatment of life-threatening infections by gram-positive bacteria. The rules by which nature assembles the glycopeptide (vancomycin) and lipoglycopeptide (teicoplanin) antibiotics are becoming elucidated and verified: first amino acids are synthesized, then joined together and cross-linked. This knowledge opens up approaches for reprogramming strategies at the level of altered monomers, swapped assembly lines, and different post-assembly tailoring enzymes. 相似文献
93.
94.
Sara Bogialli Cecilia CiampanellaRoberta Curini Antonio Di CorciaAldo Laganà 《Journal of chromatography. A》2009,1216(40):6810-6815
A simple and rapid method able to determine residues of erythromycin A, tylosin and tilmicosin in whole eggs is presented here. The analytical protocol involves a one-step extraction followed by liquid chromatography (LC)–tandem mass spectrometry. Analytes were extracted from 1 g of egg spiked with an internal standard (josamycin) with acetonitrile. In terms of accuracy, matrix effect and ion signal stability, no extract cleanup was found to be necessary. After partial solvent removal, the final extract was injected into the LC column. Extraction was effective, since absolute recovery of the analyte in egg at their maximum residue limit (MRL) level was 85–102%. Estimated limits of quantification (S/N = 10) were 0.2–0.5 ng/g. Based on the EU Commission Decision 2002/657/EC, the method was in-house validated in terms of ruggedness, specificity, linearity, within-laboratory reproducibility, decision limit (CCα) and detection capability (CCβ). The within-laboratory reproducibility, expressed as RSD (n = 18 at the MRL levels), was not higher than 13%. After validation, a short study on EA depletion in eggs was conducted after administration of this drug to laying hens. 相似文献
95.
固相萃取-超高压液相色谱-串联质谱测定水中19种抗生素 总被引:6,自引:0,他引:6
应用固相萃取(SPE)及液相色谱-串联质谱(LC-MS/MS)技术,建立了水中痕量(ng/L)四环素类、磺胺类、大环内酯类、喹诺酮类和β-内酰胺类5类共19种抗生素的同时定量检测方法。水样通过HLB萃取小柱富集后,以C18反相色谱柱为分析柱,乙腈-0.1%甲酸溶液为流动相,采用LC-MS/MS进行定量分析。选择电喷雾正电离源(ESI+),多反应监测模式(MRM),内标法定量。19种抗生素在0.5~1 000μg/L范围内均具有良好的线性关系,方法的定量下限(S/N=10,1 000倍浓缩)为0.1~0.5 ng/L。以纯水和河水(黄浦江水)作为基底,13C-咖啡因为内标物,加标质量浓度为20、100 ng/L时,抗生素的平均加标回收率分别为75%~125%和77%~132%,相对标准偏差(RSD)分别为1.7%~6.9%和0.9%~6.5%,表明所建立的测试方法准确可靠。研究结果表明,黄浦江水受到了抗生素污染,共检出15种抗生素,检出的四环素类、磺胺类、大环内酯类、喹诺酮类及β-内酰胺类抗生素污染质量浓度分别为13.0~56.9、12.2~103.4、53.8~84.8、3.1~26.2、16.5~181.6 ng/L。 相似文献
96.
Cristina Airoldi Dr. Silvia Sommaruga Dr. Silvia Merlo Paola Sperandeo Dr. Laura Cipolla Prof. Alessandra Polissi Prof. Francesco Nicotra Prof. 《Chemistry (Weinheim an der Bergstrasse, Germany)》2010,16(6):1897-1902
Lipopolysaccharide (LPS) is an essential component of the outer membrane of Gram‐negative bacteria and consists of three elements: lipid A, the core oligosaccharide, and the O‐antigen. The inner‐core region is highly conserved and contains at least one residue of 3‐deoxy‐D ‐manno‐octulosonate (Kdo). Arabinose‐5‐phosphate isomerase (API) is an aldo–keto isomerase catalyzing the reversible isomerization of D ‐ribulose‐5‐phosphate (Ru5P) to D ‐arabinose‐5‐phosphate (A5P), the first step of Kdo biosynthesis. By exploiting saturation transfer difference (STD) NMR spectroscopy, the structural requirements necessary for API substrate recognition and binding were identified, with the aim of designing new API inhibitors. In addition, simple experimental conditions for the STD experiments to perform a fast, robust, and efficient screening of small libraries of potential API inhibitors, allowing the identification of new potential leads, were set up. Due to the essential role of API enzymes in LPS biosynthesis and Gram‐negative bacteria survival, by exploiting these data, a new generation of potent antibacterial drugs could be developed. 相似文献
97.
Zou L Cheong WL Chung WH Leung YC Wong KY Wong MK Chan PH 《Chemistry (Weinheim an der Bergstrasse, Germany)》2010,16(45):13367-13371
Herein is described the development of a novel switch-on fluorescence assay for detecting β-lactamases. The fluorescence assay comprises two components: solid beads coated with a β-lactam antibiotic, which is linked to an environment-sensitive fluorophore (dansylaminothiophenol, DTA), and amyloid fibrils of hen lysozyme (acting as fluorescence enhancer and visual tool). In the presence of the clinically significant TEM-1 β-lactamase, the DTA-antibiotic complex on the solid beads is hydrolyzed, thus releasing the DTA dye into solution. The DTA dye is only weakly fluorescent in solution but gives strong green fluorescence upon binding to lysozyme fibrils. These strongly fluorescent DTA-bound fibrils can be easily visualized by the naked eye upon illumination of the sample with a simple UV lamp. The fluorescence assay can detect TEM-1 at low concentration (0.01 nM). In contrast, no observable fluorescence appears when the fluorescence assay is performed on samples without the TEM-1 β-lactamase. 相似文献
98.
99.
Bi Chen 《Analytica chimica acta》2010,674(1):89-3626
An amperometric penicillin biosensor with enhanced sensitivity was successfully developed by co-immobilization of multi-walled carbon nanotubes (MWCNTs), hematein, and β-lactamase on glassy carbon electrode using a layer-by-layer assembly technique. Under catalysis of the immobilized enzyme, penicillin was hydrolyzed, decreasing the local pH. The pH change was monitored amperometrically with hematein as a pH-sensitive redox probe. MWCNTs were used as an electron transfer enhancer as well as an efficient immobilization matrix for the sensitivity enhancement. The effects of immobilization procedure, working potential, enzyme quantity, buffer concentration, and sample matrix were investigated. The biosensor offered a minimum detection limit of 50 nM (19 μg L−1) for penicillin V, lower than those of the conventional pH change-based biosensors by more than two orders of magnitude. The electrode-to-electrode variation of the response sensitivity was 7.0% RSD. 相似文献
100.