全文获取类型
收费全文 | 1865篇 |
免费 | 78篇 |
国内免费 | 14篇 |
专业分类
化学 | 1264篇 |
晶体学 | 9篇 |
力学 | 108篇 |
数学 | 320篇 |
物理学 | 256篇 |
出版年
2024年 | 2篇 |
2023年 | 17篇 |
2022年 | 17篇 |
2021年 | 26篇 |
2020年 | 36篇 |
2019年 | 43篇 |
2018年 | 33篇 |
2017年 | 22篇 |
2016年 | 47篇 |
2015年 | 62篇 |
2014年 | 65篇 |
2013年 | 87篇 |
2012年 | 148篇 |
2011年 | 185篇 |
2010年 | 124篇 |
2009年 | 76篇 |
2008年 | 136篇 |
2007年 | 136篇 |
2006年 | 133篇 |
2005年 | 118篇 |
2004年 | 125篇 |
2003年 | 85篇 |
2002年 | 87篇 |
2001年 | 24篇 |
2000年 | 13篇 |
1999年 | 20篇 |
1998年 | 13篇 |
1997年 | 22篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1978年 | 1篇 |
排序方式: 共有1957条查询结果,搜索用时 15 毫秒
1.
2.
Chris H. Hill Agnete H. Viuff Samantha J. Spratley Stéphane Salamone Stig H. Christensen Randy J. Read Nigel W. Moriarty Henrik H. Jensen Janet E. Deane 《Chemical science》2015,6(5):3075-3086
Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease. 相似文献
3.
In this Note, we present a result concerning the non existence of linear monotone schema with fixed stencil on regular meshes for some linear parabolic equation in two dimensions. The parabolic equations of interest arise from non isotropic diffusion modelling. A corollary is that no linear monotone 9 points-schemes can be designed for the one-dimensional heat equation emerged in the plane with an arbitrary direction of diffusion. Some applications of this result are provided: for the Fokker–Planck–Lorentz model for electrons in the context of plasma physics; all linear monotone scheme for the one-dimensional hyperbolic heat equation treated as a two-dimensional problem are not consistent in the diffusion limit for an arbitrary direction of propagation. We also examine the case of the Landau equation. To cite this article: C. Buet, S. Cordier, C. R. Acad. Sci. Paris, Ser. I 340 (2005). 相似文献
4.
Luc Martinon Stéphane Azoulay E. Peter Kündig 《Journal of organometallic chemistry》2004,689(23):3831-3836
A Pd-catalyzed three-component assembling of highly functionalized 4-benzyl-(and allyl-)pyrrolidines was achieved based on a combination of allyl amines, gem-diactivated alkenes, and unsaturated halides (or triflate). 相似文献
5.
Pierre Degond Stéphane Génieys Ansgar Jüngel 《Journal de Mathématiques Pures et Appliquées》1997,76(10):991-1015
The time-dependent equations for a charged gas or fluid consisting of several components, exposed to an electric field, are considered. These equations form a system of strongly coupled, quasilinear parabolic equations which in some situations can be derived from the Boltzmann equation. The model uses the duality between the thermodynamic fluxes and the thermodynamic forces. Physically motivated mixed Dirichlet-Neumann boundary conditions and initial conditions are prescribed.The existence of weak solutions is proven. The key of the proof is (i) a transformation of the problem by using the entropic variables, or electro-chemical potentials, which symmetrizes the equations, and (ii) a priori estimates obtained by using the entropy function. Finally, the entropy inequality is employed to show the convergence of the solutions to the thermal equilibrium state as the time tends to infinity. 相似文献
6.
We consider the isothermal flow through a cylindrical flat chamber, a model of some particular heat exchanger, for which LDV measurements and a numerical simulation have been performed. Experimental results show the establishment of an important vortex zone, the secondary flow extending all along the chamber radius. This observation leads to an expected significant increase of the fluid mixing. Results issued from the numerical simulation appear to be in close agreement with experimental data. Nevertheless, the k–ε model used here must be improved to obtain a better approach near the vortex centre. To cite this article: S. Petitot et al., C. R. Mecanique 330 (2002) 593–599. 相似文献
7.
1,3-Diarylpropynones were cleanly converted to the corresponding 3-arylindenones in various superacidic media. This new, simple, one-pot reaction proved to be efficient (yields up to 95%) and very fast (reaction time less than 30 min). 相似文献
8.
We study perturbations of the Erdös–Renyi model for which the statistical weight of a graph depends on the abundance of certain geometrical patterns. Using the formal correspondance with an exactly solvable effective model, we show the existence of a percolation transition in the thermodynamical limit and derive perturbatively the expression of the threshold. The free energy and the moments of the degree distribution are also computed perturbatively in that limit and the percolation criterion is compared with the Molloy–Reed criterion. 相似文献
9.
The synthesis of enantiopure bis-THF is described, starting from d-mannitol. Bis-THF is used as chiral ligand for organolithium reagents in four different reactions. The enantioselectivity provided by this ligand is moderate, and the asymmetric induction is in line with the expected model. 相似文献
10.
We prove global existence of solutions to the continuous nonhomogeneous Smoluchowski equation for coagulation rates satisfying a more general structure condition than the Galkin–Tupchiev monotony hypothesis considered in (Ph. Laurençot, S. Mischler, Arch. Rational Mech. Anal. 162 (1) (2002) 45–99). The Smoluchowski coagulation rate fulfils this condition as well as some rates which vanish on the diagonal. Under the condition of positivity of the coagulation rate outside of the diagonal we prove that solutions tend to 0 in the large time asymptotic. These results depend on a new estimate from below for the dissipation rate of the Lp-norm, p>1. To cite this article: S. Mischler, M. Rodriguez Ricard, C. R. Acad. Sci. Paris, Ser. I 336 (2003). 相似文献