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In vitro ketamine CYP3A‐mediated metabolism study using mammalian liver S9 fractions,cDNA expressed enzymes and liquid chromatography tandem mass spectrometry 下载免费PDF全文
Raphaël Santamaria Floriane Pailleux Francis Beaudry 《Biomedical chromatography : BMC》2014,28(12):1660-1669
Ketamine is widely used in medicine in combination with several benzodiazepines, including midazolam. The objectives of this study were to develop a novel HPLC‐MS/selected reaction monitoring (SRM) method capable of quantifying ketamine and norketamine using an isotopic dilution strategy in biological matrices and study the formation of norketamine, the principal metabolite of ketamine with and without the presence of midazolam, a well‐known CYP3A substrate. The chromatographic separation was achieved using a Thermo Betasil Phenyl 100 × 2 mm column combined with an isocratic mobile phase composed of acetonitrile, methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 μL/min. The mass spectrometer was operating in selected reaction monitoring mode and the analytical range was set at 0.05–50 μm . The precision (CV) and accuracy (NOM) observed were 3.9–7.8 and 95.9–111.1% respectively. The initial rate of formation of norketamine was determined using various ketamine concentrations and Km values of 18.4, 13.8 and 30.8 μm for rat, dog and human liver S9 fractions were observed, respectively. The metabolic stability of ketamine on liver S9 fractions was significantly higher in human (T1/2 = 159.4 min) compared with rat (T1/2 = 12.6 min) and dog (T1/2 = 7.3 min) liver S9 fractions. Moreover significantly lower IC50 and Ki values observed in human compared with rat and dog liver S9 fractions. Experiments with cDNA expressed CYP3A enzymes showed that the formation of norketamine is mediated by CYP3A but results suggest an important contribution from other isoenzymes, most likely CYP2C particularly in rat. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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Malgorzata Geszke-Moritz Gilles Clavier Janina Lulek Raphaël Schneider 《Journal of luminescence》2012,132(4):987-991
3-Mercaptopropionic acid-capped core/shell ZnS:Cu/ZnS and ZnS:Mn/ZnS doped quantum dots (QDs) prepared through hydrothermal methods exhibit high photoluminescence intensity as well as good photostability. These water-dispersible nanoparticles exhibit high fluorescence sensitivity to folic acid due to the high affinity of the carboxylate groups and nitrogen atoms of folic acid towards the Zn surface atoms of the doped dots. Quenching of the fluorescence intensity of the QDs allows the detection of folic acid concentrations as low as 11 μM, thus affording a very sensitive system for the sensing of this biologically active molecule in aqueous solution. The possible quenching mechanism is discussed. 相似文献
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Raphaël Côte 《纯数学与应用数学通讯》2015,68(11):1946-2004
We consider finite energy corotational wave maps with target manifold . We prove that for a sequence of times, they decompose as a sum of decoupled harmonic maps in the light cone, and a smooth wave map (in the blowup case) or a linear scattering term (in the global case), up to an error which tends to 0 in the energy space. © 2015 Wiley Periodicals, Inc. 相似文献
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We consider L 2-critical focusing nonlinear Schrödinger equations with Hartree type nonlinearity $i \partial_{t} u = - \Delta u - \left(\Phi \ast |u|^2 \right) u \quad {\rm in}\, \mathbb {R}^4,$ where Φ(x) is a perturbation of the convolution kernel |x|?2. Despite the lack of pseudo-conformal invariance for this equation, we prove the existence of critical mass finite-time blowup solutions u(t, x) that exhibit the pseudo-conformal blowup rate $\| \nabla u(t) \|_{L^2_x}\sim \frac{1}{|t|} \quad {\rm as}\, t \nearrow 0.$ Furthermore, we prove the finite-codimensional stability of this conformal blow up, by extending the nonlinear wave operator construction by Bourgain and Wang (see Bourgain and Wang in Ann. Scuola Norm Sup Pisa Cl Sci (4) 25(1–2), 197–215, 1997/1998) to L 2-critical Hartree NLS. 相似文献
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Peptide-stabilized gold nanoparticles have been enzymatically biotinylated by a kinase-catalyzed reaction using biotin-ATP as a cosubstrate. Upon mixing with avidin-modified particles, solutions of biotinylated particles change color from red to blue, indicating aggregation of particles. On the basis of this reaction, we have developed a simple colorimetric test to monitor kinase inhibitor activity. 相似文献
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Thomas?Opitz Rapha?l?HuserEmail authorView authors OrcID profile Haakon?Bakka H?vard?Rue 《Extremes》2018,21(3):441-462
This work is motivated by the challenge organized for the 10th International Conference on Extreme-Value Analysis (EVA2017) to predict daily precipitation quantiles at the \(99.8\%\) level for each month at observed and unobserved locations. Our approach is based on a Bayesian generalized additive modeling framework that is designed to estimate complex trends in marginal extremes over space and time. First, we estimate a high non-stationary threshold using a gamma distribution for precipitation intensities that incorporates spatial and temporal random effects. Then, we use the Bernoulli and generalized Pareto (GP) distributions to model the rate and size of threshold exceedances, respectively, which we also assume to vary in space and time. The latent random effects are modeled additively using Gaussian process priors, which provide high flexibility and interpretability. We develop a penalized complexity (PC) prior specification for the tail index that shrinks the GP model towards the exponential distribution, thus preventing unrealistically heavy tails. Fast and accurate estimation of the posterior distributions is performed thanks to the integrated nested Laplace approximation (INLA). We illustrate this methodology by modeling the daily precipitation data provided by the EVA2017 challenge, which consist of observations from 40 stations in the Netherlands recorded during the period 1972–2016. Capitalizing on INLA’s fast computational capacity and powerful distributed computing resources, we conduct an extensive cross-validation study to select the model parameters that govern the smoothness of trends. Our results clearly outperform simple benchmarks and are comparable to the best-scoring approaches of the other teams. 相似文献