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 365 毫秒
1.
《Arabian Journal of Chemistry》2022,15(1):103492
Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression. A variety of chemical classes have been explored for targeting individual MMP isoforms. In the present study, we further developed our isatin based scaffold BB0223107 capable of binding to and inactivating MMP-2 in a zinc-independent manner (Agamennone et al., 2016). Forty four new compounds were synthesized based on the modified BB0223107. All compounds were tested in enzyme inhibition assays against MMP-2, ?8 and ?13. SAR studies demonstrated that 5-het(aryl)-3-aminoindolin-2-ones (37–39) were active toward MMP-2 and MMP-13. The most potent compounds 33 and 37 displayed an IC50 of 3 µM against MMP-13 and showed a negligible activity toward MMP-8; almost all new compounds were inactive toward MMP-8. Replacement of the isatin ring with a biaryl system (compound 33) did not decrease the potency against MMP-13 but reduced the selectivity. Structure-based computational studies were carried out to rationalize the inhibitory activity data. The analysis of binding geometries confirmed that all fragments occupied the S1′ site in the three enzymes while no ligand was able to bind the catalytic zinc ion. To the best of our knowledge, this is the first example of 3-aminoindolin-2-one-based MMP inhibitors that, based on the computer modeling study, do not coordinate the zinc ion. Thus, the het(aryl)-3-aminoindolin-2-one derivatives emerge as a drug-like and promising chemotype that, along with the hetaryl variations, represents an alternative and thrifty tool for chemical space exploration aimed at MMP inhibitor design. 相似文献
2.
Field-effect transistors (FETs) are one of the most widely-used electronic sensors for continuous monitoring and detection of contaminants such as pharmaceuticals and endocrine-disrupting compounds at low concentrations. FETs have been successfully utilized for the rapid analysis of these environmental pollutants due to their advantageous material properties like the disposability, rapid responses and simplicity. This paper presented an up-to-date overview of applied strategies with different bio-based materials in order to enhance the analytical performances of the designed sensors. Comparison and discussion were made between characteristics of recently engineered FET bio-sensors used for the detection of famous and selected pharmaceutical compounds in the literature. The recent progress in environmental research applications, comments on interesting trends, current challenge for future research in endocrine-disrupting chemicals’ (EDCs) detection using FETs biosensors were highlighted. 相似文献
3.
Rongzhen Wu Hongyu Chen Dr. Ninghui Chang Yuzhi Xu Prof. Dr. Jiao Jiao Prof. Dr. Hailong Zhang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(6):1166-1195
Bryostatins are a class of naturally occurring macrocyclic lactones with a unique fast developing portfolio of clinical applications, including treatment of AIDS, Alzheimer's disease, and cancer. This comprehensive account summarizes the recent progress (2014–present) in the development of bryostatins, including their total synthesis and biomedical applications. An emphasis is placed on the discussion of bryostatin 1 , the most-studied analogue to date. This review highlights the synthetic and biological challenges of bryostatins and provides an outlook on their future development. 相似文献
4.
I. L. Davies K. E. Markides M. L. Lee M. W. Raynor K. D. Bartle 《Journal of separation science》1989,12(4):193-207
Although coupled liquid chromatographygas chromatography (LC-GC) was first demonstrated ten years ago, only in the last few years has there been a sudden surge of interest in the technique. Approximately 70% of the total number of LC-GC applications have been published in the last two years (1987–88) alone. This review categorizes LC-GC publications into four main application areas: fossil fuels, foods, environmental samples, biologiical/pharmaceutical samples, and miscellaneous samples. Multidimensional separations carried out using other coupled-column chromatographic techniques (such as supercritical fluid chromatography (SFC) with GC, and on-line trace enrichment-GC) have also been included in this review. 相似文献
5.
6.
Future pathways for combinatorial chemistry 总被引:1,自引:0,他引:1
David Brown 《Molecular diversity》1997,2(4):217-222
Summary Investment in combinatorial chemistry (combichem) in the pharmaceutical industry is being driven by the need for increased efficiency. Results from pioneers in the field have demonstrated where mixture or discrete compound synthesis is useful, and what mixture sizes and compound concentrations are appropriate. To make the techniques of combichem of general utility in drug discovery, a broad range of advances is still required. Conversion of organic chemistry to solid phase conditions is key, as are developments in linkers and resins. Library design methodology requires further development. Combinatorial biosynthesis of focused libraries of natural products holds great promise for capitalising on hardwon natural product leads. Miniaturisation of screens is required to reduce the cost of screening combinatorial libraries. Developments in the processes preceding and following synthesis are required to enable the flow of increased numbers of compounds without new bottlenecks developing. The impact of combinatorial chemistry will be greatly enhanced by synergy with ongoing parallel developments in genetic technologies, screening technologies and bioinformatics. 相似文献
7.
Emrys A. Jones Nicholas P. Lockyer John C. Vickerman 《International journal of mass spectrometry》2007,260(2-3):146
Recent developments in desorption/ionisation mass spectrometry techniques have made their application to biological analysis a realistic and successful proposition. Developments in primary ion source technology, mainly through the advent of polyatomic ion beams, have meant that the technique of secondary ion mass spectrometry (SIMS) can now access the depths of information required to allow biological imaging to be a viable option.Here the role of the primary ion C60+ is assessed with regard to molecular imaging of lipids and pharmaceuticals within tissue sections. High secondary ion yields and low surface damage accumulation are demonstrated on both model and real biological samples, indicating the high secondary ion efficiency afforded to the analyst by this primary ion when compared to other cluster ion beams used in imaging. The newly developed 40 keV C60+ ion source allows the beam to be focused such that high resolution imaging is demonstrated on a tissue sample, and the greater yields allow the molecular signal from the drug raclopride to be imaged within tissue section following in vivo dosing.The localisation shown for this drug alludes to issues regarding the chemical environment affecting the ionisation probability of the molecule; the importance of this effect is demonstrated with model systems and the possibility of using laser post-ionisation as a method for reducing this consequence of bio-sample complexity is demonstrated and discussed. 相似文献
8.
This study demonstrates the separation of active ingredients in acne formulations (salicylic acid, cloramphenicol and resorcinol in presence of azulene) by capillary zone electrophoresis. Factors affecting their separations were the buffer pH and concentration, applied voltage, sample preparation, and presence of additives. Optimun results were obtained with a 50 mM sodium tetraborate-50 mM sodium phosphate, pH 9.0. The carrier electrolyte gave baseline separation with good resolution, short migration times (<6 min), great reproducibility and accuracy. Calibration plots were linear over at least three orders of magnitude of analyte concentrations, the lower limits of detection being within the range 0.39-1.25 μg ml−1. The procedure was fast and reliable and commercial pharmaceuticals could be analysed without prior sample clean-up procedure. 相似文献
9.
10.
《Electroanalysis》2005,17(20):1886-1894
Lamivudine (LAM) is a synthetic nucleoside analogue with activity against human immunodeficiency virus‐type 1 (HIV‐1) and Hepatitis B virus (HBV). The aim of this study was to determine LAM levels in serum and pharmaceutical formulations, by means of electrochemical methods using hanging mercury drop electrode (HMDE). On this electrode, LAM undergoes irreversible reduction at the peak potential near Ep?1.26 V (vs. Ag/AgCl/3 M KCl). Reduction LAM signals were measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square‐wave voltammetry (OSW). DPV and OSW techniques for the determination of LAM in acetate buffer at pH 4.5, which allows quantitation over the 4×10?6 to 1×10?4 M range in supporting electrolyte for both methods, were proposed. The linear response was obtained in acetate buffer in the ranges of 2×10?6 to 2×10?4 M for spiked serum samples at pH 4.5 for both techniques. The repeatability and reproducibility of the methods for all media were determined. The standard addition method was used in serum. Precision and accuracy were also checked in all media. No electroactive interferences from the endogenous substances were found in serum. With respect to side effects of high doses and short half‐life of LAM, a fast and simple detection method is described in this study. 相似文献