全文获取类型
收费全文 | 2827篇 |
免费 | 159篇 |
国内免费 | 25篇 |
专业分类
化学 | 2198篇 |
晶体学 | 35篇 |
力学 | 76篇 |
数学 | 152篇 |
物理学 | 550篇 |
出版年
2024年 | 2篇 |
2023年 | 14篇 |
2022年 | 53篇 |
2021年 | 58篇 |
2020年 | 58篇 |
2019年 | 51篇 |
2018年 | 40篇 |
2017年 | 34篇 |
2016年 | 93篇 |
2015年 | 84篇 |
2014年 | 91篇 |
2013年 | 159篇 |
2012年 | 223篇 |
2011年 | 251篇 |
2010年 | 163篇 |
2009年 | 137篇 |
2008年 | 226篇 |
2007年 | 202篇 |
2006年 | 179篇 |
2005年 | 171篇 |
2004年 | 119篇 |
2003年 | 98篇 |
2002年 | 102篇 |
2001年 | 61篇 |
2000年 | 43篇 |
1999年 | 49篇 |
1998年 | 23篇 |
1997年 | 19篇 |
1996年 | 32篇 |
1995年 | 29篇 |
1994年 | 24篇 |
1993年 | 24篇 |
1992年 | 12篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1976年 | 3篇 |
1974年 | 6篇 |
1972年 | 1篇 |
排序方式: 共有3011条查询结果,搜索用时 375 毫秒
61.
62.
Docking and scoring are critical issues in virtual drug screening methods. Fast and reliable methods are required for the prediction of binding affinity especially when applied to a large library of compounds. The implementation of receptor flexibility and refinement of scoring functions for this purpose are extremely challenging in terms of computational speed. Here we propose a knowledge-based multiple-conformation docking method that efficiently accommodates receptor flexibility thus permitting reliable virtual screening of large compound libraries. Starting with a small number of active compounds, a preliminary docking operation is conducted on a large ensemble of receptor conformations to select the minimal subset of receptor conformations that provides a strong correlation between the experimental binding affinity (e.g., Ki, IC50) and the docking score. Only this subset is used for subsequent multiple-conformation docking of the entire data set of library (test) compounds. In conjunction with the multiple-conformation docking procedure, a two-step scoring scheme is employed by which the optimal scoring geometries obtained from the multiple-conformation docking are re-scored by a molecular mechanics energy function including desolvation terms. To demonstrate the feasibility of this approach, we applied this integrated approach to the estrogen receptor alpha (ERalpha) system for which published binding affinity data were available for a series of structurally diverse chemicals. The statistical correlation between docking scores and experimental values was significantly improved from those of single-conformation dockings. This approach led to substantial enrichment of the virtual screening conducted on mixtures of active and inactive ERalpha compounds. 相似文献
63.
We have developed a strategy of signal generation for immunosensors that transduces biospecific affinity recognition reactions into electrochemical signals. The cyclic voltammetric method, tracking the precipitation of insoluble products onto the sensing surface and the subsequent decrement in the electrode area, was chosen for signal registration. Precipitation of insolubilities was induced by the catalytic reaction of enzymes, which were labeled to the biospecifically attached protein or antibody molecules. As a model system for affinity recognition, we have investigated the functionalization of biotin groups to the sensing monolayer and their biospecific interactions with anti-biotin antibody molecules. The immunosensing interface was developed onto the dendrimer-activated self-assembled monolayers (SAMs), as the base template for the functionalization of the antigen moiety and signal generation. The advantages of using dendrimer-activated SAMs in comparison to the plain modified thiolate SAMs for the sensing surface were shown in terms of sensing performances, and the analytical characteristics of the resulting immunosensor were examined. Additionally, the sensing system was applied for biotin/(strept)avidin couples, extending the applicability of the developed strategy. 相似文献
64.
65.
Some photosensitive molecules, such as p-N,N′-dimethylaminobenzoic acid (DMABA), Nile Red, heteropolytungstic acid (H3PW12O40, HPA) and metalloporphyrins, have been entrapped onto nano-scale pores or channels of TiO2-modified Y-Zeolite (TiO2-Y-Zeolite) and MCM41 (TiO2-MCM41) and their excited-state intermediates have been characterized in terms of the excited-state dynamics by using laser spectroscopic techniques. Through these studies, it has been found that the photo-induced electrons are generated from the intramolecular charge transfer (ICT) state of DMABA, Nile Red or metalloporphyrin (MnTPP(Cl)), followed by transferring to the TiO2-Y-Zeolite or TiO2-MCM41 more efficiently as compared to the bulk TiO2, NaY-Zeolite or MCM41. The efficient photoinduced interfacial electron transfer causes the rapid formation of radicals of those photosensitive molecules (a few tens ps). It has been also found that these photophysical properties can be applied to develop the new photocatalyst as observed by the efficient photocatalytic activities of the DMABA or Nile Red-entrapped TiO2-Y-Zeolites for the photoreduction of an azo-dye such as Methyl Orange in water. On the other hand, in case of HPA-entrapped TiO2-Y-zeolite, the electron generated from the excited-state TiO2 is transferred to HPA, followed by formation of the reduction product, heteropoly blue (HPB) which is also generated by UV irradiation of HPA. This electron transfer is analogous to the Z-scheme mechanism of plant photosynthetic systems showing two photon reactions. Because of this photoelectron transfer mechanism, the HPA-entrapped TiO2-Y-zeolite has demonstrated the synergistic enhancement of the photocatalytic decomposition of Methyl Orange and hydrogen generation from photolysis of water. 相似文献
66.
Xanthine Sensors Based on Anodic and Cathodic Detection of Enzymatically Generated Hydrogen Peroxide
A xanthine biosensor was fabricated by the covalent immobilization of xanthine oxidase (XO) onto a functionalized conducting polymer (Poly‐5, 2′: 5′, 2″‐terthiophine‐3‐carboxylic acid), poly‐TTCA through the formation of amide bond between carboxylic acid groups of poly‐TTCA and amine groups of enzyme. The immobilization of XO onto the conducting polymer (XO/poly‐TTCA) was characterized using cyclic voltammetry, quartz crystal microbalance (QCM), and X‐ray photoelectron spectroscopy (XPS) techniques. The direct electron transfer of the immobilized XO at poly‐TTCA was found to be quasireversible and the electron transfer rate constant was determined to be 0.73 s?1. The biosensor efficiently detected xanthine through oxidation at +0.35 V and reduction at ?0.25 V (versus Ag/AgCl) of enzymatically generated hydrogen peroxide. Various experimental parameters, such as pH, temperature, and applied potential were optimized. The linear dynamic ranges of anodic and cathodic detections of xanthine were between 5.0×10?6?1.0×10?4 M and 5.0×10?7 to 1.0×10?4 M, respectively. The detection limits were determined to be of 1.0×10?6 M and 9.0×10?8 M with anodic and cathodic processes, respectively. The applicability of the biosensor was tested by detecting xanthine in blood serum and urine real samples. 相似文献
67.
Koketsu M Choi SY Ishihara H Lim BO Kim H Kim SY 《Chemical & pharmaceutical bulletin》2002,50(12):1594-1596
This study reports depigmenting potency of 1,3-selenazol-4-one derivatives, which would be based upon the finding of direct inhibition to mushroom tyrosinase. 1,3-Selenazol-4-one derivatives exhibited inhibitory effect on dopa oxidase activity of mushroom tyrosinase. In this study, inhibitory effects of six kinds of 1,3-selenazol-4-one derivatives (A, B, C, D, E and F) on mushroom tyrosinase were investigated. Compounds at a concentration of 500 microM exhibited 33.4-62.1% of inhibition on dopa oxidase activity of mushroom tyrosinase. Their inhibitory effects were higher than that of kojic acid (31.7%), a well known tyrosinase inhibitor. 2-(4-Methylphenyl)-1,3-selenazol-4-one (A) exhibited the strongest inhibitory effect among them dose-dependently and in competitive inhibition manner. 相似文献
68.
Abstract— The photocycloaddition reaction of 5,7-dimethoxycoumarin to thymidine on direct irradiation (λ > 300 nm) is studied as a model for photosensitization reaction of furocoumarins. The major photoadducts were isolated by silica gel column and gel permeation chromatography. Each component of the photoadducts was further separated by reverse phase, paired-ion high performance liquid chromatography. The structure of these photoproducts isolated is consistent with 1:1 C4 -cycloadducts in accordance with characteristics of their UV, IR, NMR and mass spectra and elemental analysis data. The stereochemistry of each isomer was studied by Fourier transform NMR, UV and IR spectra. The fraction C has the anti head-to-tail configuration and the fraction D has the configuration of anti head-to-head. The fractions A and B probably have the syn configuration. 相似文献
69.
Xiaofeng Wu Jong Min An Jizhen Shang Eugene Huh Sujie Qi Eunhye Lee Haidong Li Gyoungmi Kim Huimin Ma Myung Sook Oh Dokyoung Kim Juyoung Yoon 《Chemical science》2020,11(41):11285
Acetylcholinesterase (AChE) is an extremely critical hydrolase tightly associated with neurological diseases. Currently, developing specific substrates for imaging AChE activity still remains a great challenge due to the interference from butyrylcholinesterase (BChE) and carboxylesterase (CE). Herein, we propose an approach to designing specific substrates for AChE detection by combining dimethylcarbamate choline with a self-immolative scaffold. The representative P10 can effectively eliminate the interference from CE and BChE. The high specificity of P10 has been proved via imaging AChE activity in cells. Moreover, P10 can also be used to successfully map AChE activity in different regions of a normal mouse brain, which may provide important data for AChE evaluation in clinical studies. Such a rational and effective approach can also provide a solid basis for designing probes with different properties to study AChE in biosystems and another way to design specific substrates for other enzymes.In this work, a new approach was developed for designing the representative P10 with high selectivity and sensitivity for imaging AChE activity in the cells and normal mouse brain. 相似文献
70.
Some azeto[2,1-a]isoquinolin-2-ones were synthesized from 2-(3,4-dimethoxyphenyl)ethylamine in three steps in good yield. 相似文献