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961.
Berzas Nevado JJ Villaseñor Llerena MJ Guiberteau Cabanillas C Rodríguez Robledo V Buitrago S 《Journal of separation science》2006,29(1):103-113
A simple, fast, selective and very sensitive capillary GC-MS method for the simultaneous determination of five antidepressant drugs is described. Fluoxetine, fluvoxamine, citalopram, sertraline and paroxetine belong to the newest and most important drug group termed selective serotonin reuptake inhibitors. Imipramine was used in this method as an internal standard for quantification. Optimum parameters for GC separation were investigated, i.e., flow rate, column head pressure, injector temperature, injection splitless conditions and oven temperature program. MS detection was performed in SIM mode to increase the sensitivity. Stability of the solutions, linear concentration range, accuracy, precision, LOD, LOQ (3.6-41.5 mg/L) and specificity were examined in the presence of excipients for checking the reliability of this method. The robustness was evaluated with a matrix of 15 experiments (seven factors and three levels) using Plackett-Burman fractional factorial experimental design, and Youden and Steiner statistical treatment. The method was applied to the analysis of these antidepressants in nearly all their pharmaceutical formulations, obtaining recoveries between 98.1% and 102.7% with regard to the claimed values. 相似文献
962.
Jill E. Hochlowski Jeffrey Y. PanPhilip A. Searle Wayne R. BuckStephen G. Spanton 《Journal of chromatography. A》2009,1216(34):6162-6169
Experiments were performed to demonstrate the potential of counter-current chromatography (CCC) for the isolation of drugs and their metabolites from biological matrices relevant to the metabolism studies of pharmaceutical research. Examples of typical drugs are spiked into biological media ex vivo to provide test samples for analysis. A mass spectrometer hyphenated to a CCC allows for the detection of small molecule drugs within the matrix through selected ion monitoring, and fraction collection can provide material for further structural elucidation by NMR. 相似文献
963.
In this work, an on-line system with vapor-phase generation (VPG) and Fourier transform infrared (FTIR) spectrometric detection has been developed as a direct and highly selective analytical technique for the assay of penicillamine (PA). Potassium iodate solution was injected into a reactor, heated at 75 °C, containing PA. The CO generated under these conditions was transported by means of N2 gas carrier stream to an infrared gas cell and corresponding FTIR spectra were acquired in a continuous mode. The maximum absorbance of CO band at 2170 cm−1, corrected by a baseline established between 2240 and 2000 cm−1 at a nominal resolution of 2 cm−1, was selected as a measurement criterion. Initially, the effect of different chemical, physical and spectroscopic parameters, such as concentration and volume of oxidant, pH, equilibrium time, reactor temperature, reactor volume, N2 carrier flow rate and number of scans on the analytical signals were evaluated by using a short path length (10 cm) IR gas cell. At optimum experimental conditions, the method provided a relatively broad linear dynamic range of 4-380 mg L−1, a limit of detection of 0.5 mg L−1, a sampling frequency of 15 h−1 and a relative standard deviation (R.S.D.) of 1.6%. Further, the method was successfully applied to the determination of PA in pharmaceutical formulations and results compared well with those obtained by a reference colorimetric method. 相似文献
964.
Hähnke V Hofmann B Grgat T Proschak E Steinhilber D Schneider G 《Journal of computational chemistry》2009,30(5):761-771
We present a ligand-based virtual screening technique (PhAST) for rapid hit and lead structure searching in large compound databases. Molecules are represented as strings encoding the distribution of pharmacophoric features on the molecular graph. In contrast to other text-based methods using SMILES strings, we introduce a new form of text representation that describes the pharmacophore of molecules. This string representation opens the opportunity for revealing functional similarity between molecules by sequence alignment techniques in analogy to homology searching in protein or nucleic acid sequence databases. We favorably compared PhAST with other current ligand-based virtual screening methods in a retrospective analysis using the BEDROC metric. In a prospective application, PhAST identified two novel inhibitors of 5-lipoxygenase product formation with minimal experimental effort. This outcome demonstrates the applicability of PhAST to drug discovery projects and provides an innovative concept of sequence-based compound screening with substantial scaffold hopping potential. 相似文献
965.
Niklas Blomberg David A. Cosgrove Peter W. Kenny Karin Kolmodin 《Journal of computer-aided molecular design》2009,23(8):513-525
Approaches to the design of libraries for fragment screening are illustrated with reference to a 20 k generic fragment screening
library and a 1.2 k generic NMR screening library. Tools and methods for library design that have been developed within AstraZeneca
are described, including Foyfi fingerprints and the Flush program for neighborhood characterization. It will be shown how
Flush and the BigPicker, which selects maximally diverse sets of compounds, are used to apply the Core and Layer method for
library design. Approaches to partitioning libraries into cocktails are also described. 相似文献
966.
967.
Günter Mayer Dr. 《Angewandte Chemie (International ed. in English)》2009,48(15):2672-2689
Taking a strand : Aptamers are small single‐stranded oligonucleotides that fold into a well‐defined 3D structure and interact with high affinity and specificity with their target molecules, thereby inhibiting their biological functions. Aptamers can be synthesized by either chemical and/or enzymatic procedures and can thus be considered as both chemical and biological substances. The current status and new developments in this area are described.
968.
Dieter Haebich Dr. Franz von Nussbaum Dr. 《Angewandte Chemie (International ed. in English)》2009,48(19):3397-3400
Form and function : The natural product myxopyronin A provides the key to understanding the inhibition of bacterial RNA polymerase and should spark new ideas for the design of new antibiotics against tuberculosis and other infectious diseases.
969.
Albert Koulman Geoffrey A. Lane Scott J. Harrison Dietrich A. Volmer 《Analytical and bioanalytical chemistry》2009,394(3):663-670
The current developments in metabolomics and metabolic profiling technologies have led to the discovery of several new metabolic
biomarkers. Finding metabolites present in significantly different levels between sample sets, however, does not necessarily
make these metabolites useful biomarkers. The route to valid and applicable biomarkers (biomarker qualification) is long and
demands a significant amount of work. In this overview, we critically discuss the current state-of-the-art of metabolic biomarker
discovery, with highlights and shortcomings, and suggest a pathway to clinical usefulness.
相似文献
Dietrich A. VolmerEmail: |
970.
There is an urgent need to find new antibacterial agents to combat bacterial infections, including agents that inhibit novel, hitherto unexploited targets in bacterial cells. Amongst novel targets are two-component signal transduction systems (TCSs) which are the main mechanism by which bacteria sense and respond to environmental changes. TCSs typically comprise a membrane-embedded sensory protein (the sensor histidine kinase, SHK) and a partner response regulator protein. Amongst promising targets within SHKs are those involved in environmental signal detection (useful for targeting specific SHKs) and the common themes of signal transmission across the membrane and propagation to catalytic domains (for targeting multiple SHKs). However, the nature of environmental signals for the vast majority of SHKs is still lacking, and there is a paucity of structural information based on full-length membrane-bound SHKs with and without ligand. Reasons for this lack of knowledge lie in the technical challenges associated with investigations of these relatively hydrophobic membrane proteins and the inherent flexibility of these multidomain proteins that reduces the chances of successful crystallisation for structural determination by X-ray crystallography. However, in recent years there has been an explosion of information published on (a) methodology for producing active forms of full-length detergent-, liposome- and nanodisc-solubilised membrane SHKs and their use in structural studies and identification of signalling ligands and inhibitors; and (b) mechanisms of signal sensing and transduction across the membrane obtained using sensory and transmembrane domains in isolation, which reveal some commonalities as well as unique features. Here we review the most recent advances in these areas and highlight those of potential use in future strategies for antibiotic discovery. This Review is part of a Special Issue entitled “Interactions of Bacterial Molecules with Their Ligands and Other Chemical Agents” edited by Mary K. Phillips-Jones. 相似文献