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61.
Lucie Nováková Vincent Desfontaine Federico Ponzetto Raul Nicoli Martial Saugy Jean-Luc Veuthey Davy Guillarme 《Analytica chimica acta》2016
This study shows the possibility offered by modern ultra-high performance supercritical fluid chromatography combined with tandem mass spectrometry in doping control analysis. A high throughput screening method was developed for 100 substances belonging to the challenging classes of anabolic agents, hormones and metabolic modulators, synthetic cannabinoids and glucocorticoids, which should be detected at low concentrations in urine. To selectively extract these doping agents from urine, a supported liquid extraction procedure was implemented in a 48-well plate format. At the tested concentration levels ranging from 0.5 to 5 ng/mL, the recoveries were better than 70% for 48–68% of the compounds and higher than 50% for 83–87% of the tested substances. Due to the numerous interferences related to isomers of steroids and ions produced by the loss of water in the electrospray source, the choice of SFC separation conditions was very challenging. After careful optimization, a Diol stationary phase was employed. The total analysis time for the screening assay was only 8 min, and interferences as well as susceptibility to matrix effect (ME) were minimized. With the developed method, about 70% of the compounds had relative ME within the range ±20%, at a concentration of 1 and 5 ng/mL. Finally, limits of detection achieved with the above-described strategy including 5-fold preconcentration were below 0.1 ng/mL for the majority of the tested compounds. Therefore, LODs were systematically better than the minimum required performance levels established by the World anti-doping agency, except for very few metabolites. 相似文献
62.
Jean-Luc Veuthey 《Analytical and bioanalytical chemistry》2010,396(7):2377-2378
63.
The aim of this work was to develop a trypsin-based micro-immobilized enzyme reactor prepared on a monolithic ethylenediamine BIA Separations CIM (convective interaction media) minidisk. The micro-immobilized enzyme reactor (IMER) was integrated in a liquid chromatography system hyphenated to electrospray ionization tandem mass spectrometry to carry out on-line protein digestion and identification. The performance of this IMER was compared with that obtained using a previously developed bioreactor prepared on a conventional CIM ethylenediamine disk and with that of the commercially available Poroszyme immobilized trypsin cartridge. In this work, we showed how different proteins were identified with good recoveries using a digestion time of 10 min only. 相似文献
64.
Successive oxidation of transition metal(II) aqua complexes (M(II)OH(2) to M(III)OH) is a domain in which proton-coupled electron transfer reactions are extremely common. The mechanism of these PCET reactions-concerted or stepwise-is an important issue in the understanding and design of natural or artificial systems catalyzing the formation of dioxygen by four-electron oxidation of water. Concerted proton-coupled electron transfer from an aqua metal(II) to a hydroxo metal(III) complex requires the close proximity of a proton-accepting group with a pK value between those of the aqua complexes. Otherwise, stepwise electron-proton or proton-electron pathways involving high-energy intermediates are followed. Concerted proton-electron pathways involving water as proton-acceptor or proton-donor group are inefficient. Cyclic voltammetry of the title complex in buffered aqueous solution and re-examination of previous results for the same complex attached to an electrode surface are used to establish these conclusions, which provide a starting point on the route to higher degrees of oxidation, such as those involved in the catalysis of water oxidation. 相似文献
65.
Yveline Henchoz Bruno Bard Davy Guillarme Pierre-Alain Carrupt Jean-Luc Veuthey Sophie Martel 《Analytical and bioanalytical chemistry》2009,394(3):707-729
The measurement of physicochemical properties at an early phase of drug discovery and development is crucial to reduce attrition
rates due to poor biopharmaceutical properties. Among these properties, ionization, lipophilicity, solubility and permeability
are mandatory to predict the pharmacokinetic behavior of NCEs (new chemical entities). Due to the high number of NCEs, the
analytical tools used to measure these properties are automated and progressively adapted to high-throughput technologies.
The present review is dedicated to experimental methods applied in the early drug discovery process for the determination
of solubility, ionization constants, lipophilicity and permeability of small molecules. The principles and experimental conditions
of the different methods are described, and important enhancements in terms of throughput are highlighted.
Figure Scheme of the Drug Research Process. 相似文献
66.
Yveline Henchoz Davy Guillarme Sophie Martel Serge Rudaz Jean-Luc Veuthey Pierre-Alain Carrupt 《Analytical and bioanalytical chemistry》2009,394(7):1919-1930
Ultra-high-pressure liquid chromatography (UHPLC) systems able to work with columns packed with sub-2 μm particles offer very
fast methods to determine the lipophilicity of new chemical entities. The careful development of the most suitable experimental
conditions presented here will help medicinal chemists for high-throughput screening (HTS) log P
oct measurements. The approach was optimized using a well-balanced set of 38 model compounds and a series of 28 basic compounds
such as β-blockers, local anesthetics, piperazines, clonidine, and derivatives. Different organic modifiers and hybrid stationary
phases packed with 1.7-μm particles were evaluated in isocratic as well as gradient modes, and the advantages and limitations
of tested conditions pointed out. The UHPLC approach offered a significant enhancement over the classical HPLC methods, by
a factor 50 in the lipophilicity determination throughput. The hyphenation of UHPLC with MS detection allowed a further increase
in the throughput. Data and results reported herein prove that the UHPLC-MS method can represent a progress in the HTS-measurement
of lipophilicity due to its speed (at least a factor of 500 with respect to HPLC approaches) and to an extended field of application.
Figure The UHPLC approach described here greatly enhanced the time required for log P determination (5' min by compound using UV
detection) and, at least, 8 compounds measured in a 5' run when Mass Spectrometry detection in used. These developments offer
to medicinal chemists a high-throughput method to estimate the lipophilicity of NCEs
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Experimental section for capillary electrophoresis
(CE) measurements, list of the 38 compounds of the calibration set and solvatochromic analyses of the extrapolated retention
factors and partition coefficients. 相似文献
67.
New trends in fast and high-resolution liquid chromatography: a critical comparison of existing approaches 总被引:1,自引:0,他引:1
Davy Guillarme Josephine Ruta Serge Rudaz Jean-Luc Veuthey 《Analytical and bioanalytical chemistry》2010,397(3):1069-1082
Recent developments in chromatographic supports and instrumentation for liquid chromatography (LC) are enabling rapid and
highly efficient separations. Various analytical strategies have been proposed, for example the use of silica-based monolithic
supports, elevated mobile phase temperatures, and columns packed with sub-3 μm superficially porous particles (fused core)
or with sub-2 μm porous particles for use in ultra-high-pressure LC (UHPLC). The purpose of this review is to describe and
compare these approaches in terms of throughput and resolving power, using kinetic data gathered for compounds with molecular
weights ranging between 200 and 1300 g mol−1 in isocratic and gradient modes. This study demonstrates that the best analytical strategy should be selected on the basis
of the analytical problem (e.g., isocratic vs. gradient, throughput vs. efficiency) and the properties of the analyte. UHPLC
and fused-core technologies are quite promising for small-molecular-weight compounds, but increasing the mobile phase temperature
is useful for larger molecules, for example peptides. 相似文献
68.
An effective combination of focused microwave-assisted extraction (FMAE) with solid-phase microextraction (SPME) prior to gas chromatography (GC) is described for the selective extraction and quantitative analysis of cocaine from coca leaves (Erythroxylum coca). This approach required switching from an organic extraction solvent to an aqueous medium more compatible with SPME liquid sampling. SPME was performed in the direct immersion mode with a universal 100 microm polydimethylsiloxane (PDMS) coated fibre. Parameters influencing this extraction step, such as solution pH, sampling time and temperature are discussed. Furthermore, the overall extraction process takes into account the stability of cocaine in alkaline aqueous solutions at different temperatures. Cocaine degradation rate was determined by capillary electrophoresis using the short end injection procedure. In the selected extraction conditions, less than 5% of cocaine was degraded after 60 min. From a qualitative point of view, a significant gain in selectivity was obtained with the incorporation of SPME in the extraction procedure. As a consequence of SPME clean-up, shorter columns could be used and analysis time was reduced to 6 min compared to 35 min with conventional GC. Quantitative results led to a cocaine content of 0.70 +/- 0.04% in dry leaves (RSD <5%) which agreed with previous investigations. 相似文献
69.
Badoud F Grata E Boccard J Guillarme D Veuthey JL Rudaz S Saugy M 《Analytical and bioanalytical chemistry》2011,400(2):503-516
The urinary steroid profile is constituted by anabolic androgenic steroids, including testosterone and its relatives, that
are extensively metabolized into phase II sulfated or glucuronidated steroids. The use of liquid chromatography coupled to
mass spectrometry (LC-MS) is an issue for the direct analysis of conjugated steroids, which can be used as urinary markers
of exogenous steroid administration in doping analysis, without hydrolysis of the conjugated moiety. In this study, a sensitive
and selective ultra high-pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS)
method was developed to quantify major urinary metabolites simultaneously after testosterone intake. The sample preparation
of the urine (1 mL) was performed by solid-phase extraction on Oasis HLB sorbent using a 96-well plate format. The conjugated
steroids were analyzed by UHPLC-QTOF-MSE with a single-gradient elution of 36 min (including re-equilibration time) in the negative electrospray ionization mode.
MSE analysis involved parallel alternating acquisitions of both low- and high-collision energy functions. The method was validated
and applied to samples collected from a clinical study performed with a group of healthy human volunteers who had taken testosterone,
which were compared with samples from a placebo group. Quantitative results were also compared to GC-MS and LC-MS/MS measurements,
and the correlations between data were found appropriate. The acquisition of full mass spectra over the entire mass range
with QTOF mass analyzers gives promise of the opportunity to extend the steroid profile to a higher number of conjugated steroids. 相似文献
70.
为研究超高韧性水泥基复合材料(ultra-high toughness cementitious composites, UHTCC)在内埋炸药爆炸下的抗爆性能和损伤破坏规律,对不同炸药埋深下的UHTCC和高强混凝土(high-strength concrete, HSC)进行了内埋炸药抗爆实验。得到了两种材料靶体的破坏状态,并利用接触爆炸的实验结果计算出了两种材料的抗爆性能参数。结果表明,在相同条件下,UHTCC抗爆性能优于高强混凝土。为了进一步探究UHTCC的抗压强度、抗拉强度以及拉伸韧性对靶体在内埋炸药下抗爆性能的影响,首先,采用改进的K&C模型对炸药埋深为40 mm的超高韧性水泥基复合材料靶体进行数值模拟,模拟结果与实验结果基本吻合,并根据数值模拟的结果得到了爆炸冲击波沿靶体径向衰减速度大于轴向衰减速度这一规律,验证了数值模型的有效性;然后,通过调整改进K&C模型中与抗压强度、抗拉强度以及拉伸韧性相关的参数,数值预测了不同抗压强度、抗拉强度以及拉伸韧性下UHTCC靶体的破坏状态,发现增强UHTCC的韧性可以有效防止靶体发生整体性破坏,增大UHTCC的抗拉强度可以减小靶体迎爆面的开坑直径,增大UHTCC的抗压强度对减小开坑直径效果不明显。 相似文献