全文获取类型
收费全文 | 5015篇 |
免费 | 151篇 |
国内免费 | 60篇 |
专业分类
化学 | 2943篇 |
晶体学 | 26篇 |
力学 | 167篇 |
数学 | 830篇 |
物理学 | 1260篇 |
出版年
2023年 | 28篇 |
2022年 | 116篇 |
2021年 | 138篇 |
2020年 | 137篇 |
2019年 | 133篇 |
2018年 | 152篇 |
2017年 | 115篇 |
2016年 | 202篇 |
2015年 | 132篇 |
2014年 | 172篇 |
2013年 | 307篇 |
2012年 | 327篇 |
2011年 | 335篇 |
2010年 | 231篇 |
2009年 | 200篇 |
2008年 | 302篇 |
2007年 | 256篇 |
2006年 | 303篇 |
2005年 | 273篇 |
2004年 | 211篇 |
2003年 | 164篇 |
2002年 | 145篇 |
2001年 | 88篇 |
2000年 | 67篇 |
1999年 | 66篇 |
1998年 | 45篇 |
1997年 | 41篇 |
1996年 | 31篇 |
1995年 | 28篇 |
1994年 | 31篇 |
1993年 | 21篇 |
1992年 | 23篇 |
1991年 | 29篇 |
1990年 | 13篇 |
1989年 | 13篇 |
1988年 | 13篇 |
1986年 | 16篇 |
1985年 | 27篇 |
1984年 | 19篇 |
1983年 | 21篇 |
1982年 | 19篇 |
1981年 | 21篇 |
1980年 | 22篇 |
1979年 | 16篇 |
1978年 | 15篇 |
1977年 | 17篇 |
1975年 | 16篇 |
1974年 | 21篇 |
1973年 | 12篇 |
1971年 | 13篇 |
排序方式: 共有5226条查询结果,搜索用时 15 毫秒
71.
Igor Dovgan Alexandre Hentz Oleksandr Koniev Anthony Ehkirch Steve Hessmann Sylvain Ursuegui Sbastien Delacroix Margaux Riomet Frdric Taran Sarah Cianfrani Sergii Kolodych Alain Wagner 《Chemical science》2020,11(5):1210
Controlled protein functionalization holds great promise for a wide variety of applications. However, despite intensive research, the stoichiometry of the functionalization reaction remains difficult to control due to the inherent stochasticity of the conjugation process. Classical approaches that exploit peculiar structural features of specific protein substrates, or introduce reactive handles via mutagenesis, are by essence limited in scope or require substantial protein reengineering. We herein present equimolar native chemical tagging (ENACT), which precisely controls the stoichiometry of inherently random conjugation reactions by combining iterative low-conversion chemical modification, process automation, and bioorthogonal trans-tagging. We discuss the broad applicability of this conjugation process to a variety of protein substrates and payloads.Controlled protein functionalization holds great promise for a wide variety of applications.Applications of protein conjugates are limitless, including imaging, diagnostics, drug delivery, and sensing.1–4 In many of these applications, it is crucial that the conjugates are homogeneous.5 The site-selectivity of the conjugation process and the number of functional labels per biomolecule, known as the degree of conjugation (DoC), are crucial parameters that define the composition of the obtained products and are often the limiting factors to achieving adequate performance of the conjugates. For instance, immuno-PCR, an extremely sensitive detection technique, requires rigorous control of the average number of oligonucleotide labels per biomolecule (its DoC) in order to achieve high sensitivity.6 In optical imaging, the performance of many super-resolution microscopy techniques is directly defined by the DoC of fluorescent tags.7 For therapeutics, an even more striking example is provided by antibody–drug conjugates, which are prescribed for the treatment of an increasing range of cancer indications.8 A growing body of evidence from clinical trials indicates that bioconjugation parameters, DoC and DoC distribution, directly influence the therapeutic index of these targeted agents and hence must be tightly controlled.9Standard bioconjugation techniques, which rely on nucleophile–electrophile reactions, result in a broad distribution of different DoC species (Fig. 1a), which have different biophysical parameters, and consequently different functional properties.10Open in a separate windowFig. 1Schematic representation of the types of protein conjugates.To address this key issue and achieve better DoC selectivity, a number of site-specific conjugation approaches have been developed (Fig. 1b). These techniques rely on protein engineering for the introduction of specific motifs (e.g., free cysteines,11 selenocysteines,12 non-natural amino acids,13,14 peptide tags recognized by specific enzymes15,16) with distinct reactivity compared to the reactivity of the amino acids present in the native protein. These motifs are used to simultaneously control the DoC (via chemo-selective reactions) and the site of payload attachment. Both parameters are known to influence the biological and biophysical parameters of the conjugates,11 but so far there has been no way of evaluating their impact separately.The influence of DoC is more straightforward, with a lower DoC allowing the minimization of the influence of payload conjugation on the properties of the protein substrate. The lowest DoC that can be achieved for an individual conjugate is 1 (corresponding to one payload attached per biomolecule). It is noteworthy that DoC 1 is often difficult to achieve through site-specific conjugation techniques due to the symmetry of many protein substrates (e.g., antibodies). Site selection is a more intricate process, which usually relies on a systematic screening of conjugation sites for some specific criteria, such as stability or reactivity.17Herein, we introduce a method of accessing an entirely new class of protein conjugates with multiple conjugation sites but strictly homogenous DoCs (Fig. 1c). To achieve this, we combined (a) iterative low conversion chemical modification, (b) process automation, and (c) bioorthogonal trans-tagging in one workflow.The method has been exemplified for protein substrates, but it is applicable to virtually any native bio-macromolecule and payload. Importantly, this method allows for the first time the disentangling of the effects of homogeneous DoC and site-specificity on conjugate properties, which is especially intriguing in the light of recent publications revealing the complexity of the interplay between payload conjugation sites and DoC for in vivo efficacy of therapeutic bioconjugates.18 Finally, it is noteworthy that this method can be readily combined with an emerging class of site-selective bioconjugation reagents to produce site-specific DoC 1 conjugates, thus further expanding their potential for biotechnology applications.19 相似文献
72.
Gschwind RM Armbrüster M Zubrzycki IZ 《Journal of the American Chemical Society》2004,126(33):10228-10229
Hydrogen bonding plays a major role in the selective recognition of guanidinium groups by receptor molecules. The present NMR investigation provides direct experimental evidence of hydrogen bonds in an artificial arginine receptor complex consisting of alpha-N-benzoylarginine ethyl ester and a bisphosphonate tweezers molecule. trans-Hydrogen bond 2hJHP couplings between the phosphonate moieties and individual guanidinium protons as well as the amide proton have been detected by [1H,31P]-HMBC and [31P,1H]-INEPT experiments. The detected hydrogen bonding network in the investigated artificial arginine receptor shows a symmetrical end-on interaction of the guanidinium moiety, which enables concerted rotations and deviates from the structure proposed for the biological arginine fork. 相似文献
73.
The structural parameters of 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX), (CH2NNO2)3, 1,3-dinitro-1,3-diazacyclopentane (DDCP), CH2(CH2NNO2)2, andN-nitropyrrolidine (NP), (CH2)4NNO2, have been determined by electron diffraction.The six-membered ring of RDX has a chair form with axial positions of the nitro groups and close to planar bond geometry of the amine nitrogen atoms. The overallC
3 symmetry of the molecule is in agreement with the experimental data.The conformation of the five-membered ring in DDCP is a half-chair ofC
2 symmetry, while that in NP is an envelope ofC
S symmetry. The nitro groups are in equatorial positions in both molecules. The conformations of pyrrolidine and imidazolidine cycles show interesting features.The pyramidal geometry of the amine nitrogen atom bonds flattens in going from pyrrolidine andN-chloropyrrolidine to NP and DDCP and then to RDX and to dimethylnitramine (DMNA), (CH3)2NNO2. 相似文献
74.
BIT Numerical Mathematics - In this paper we propose a method to compute the solution to the fractional diffusion equation on directed networks, which can be expressed in terms of the graph... 相似文献
75.
Ann M. Schmiedekamp Igor A. Topol Stanley K. Burt Holy Razafinjanahary Henry Chermette Timothy Pfaltzgraff Christopher J. Michejda 《Journal of computational chemistry》1994,15(8):875-892
The consistency of three density functional computational implementations (DMol, DGauss, and deMon) are compared with high-level Hartree–Fock and Møller–Plesset (MP) calculations for triazene (HN?NNH2) and formyl triazene (HN?NNHCOH). Proton affinities on all electronegative sites are investigated as well as the geometries of the neutral and protonated species. Density functional calculations employing the nonlocal gradient corrections show agreement with MP calculations for both proton affinities and geometries of neutral and protonated triazenes. Local spin density approximation DMol calculations using numerical basis sets must employ an extended basis to agree with other density functional codes using analytic Gaussian basis sets. The lowest energy conformation of triazene was found to be nonplanar; however, the degree of nonplanarity, as well as some bond lengths, is dependent on the basis set, electron correlation treatment, and methods used for the calculation. © 1994 by John Wiley & Sons, Inc. 1 This article is a U.S. Government work and, as such, is in the public domain in the United States of America. 相似文献
76.
We prove that certain two-point Padé approximants occupying the diagonal of the Padé table form monotone sequences of lower and upper bounds uniformly converging to a Stieltjes function. The results can be applied to the theory of inhomogeneous media for the calculation of the bounds on the effective transport coefficients of heterogeneous materials. 相似文献
77.
78.
We establish an explicit isomorphism between two realizations of the quantum affine algebra
given previously by Drinfeld and Reshetikhin-Semenov-Tian-Shansky. Our result can be considered as an affine version of the isomorphism between the Drinfield/Jimbo and the Faddeev-Reshetikhin-Takhtajan constructions of the quantum algebra
. 相似文献
79.
I. E. Baranov S. A. Demkin V. K. Zhivotov I. I. Nikolaev V. D. Rusanov N. G. Fedotov 《High Energy Chemistry》2004,38(3):191-195
A method for enhancing the hydrocarbon pyrolysis process by introducing atomic hydrogen into the reaction medium from an arcjet plasma source was considered. It was shown that hydrogen atoms could effectively be introduced by mixing under low pressure. The atomic hydrogen–stimulated methane pyrolysis process was experimentally studied in a continuous stirred reactor with a plasma plume. When hydrogen atoms were present in the plasma jet, the amount of the valuable product increased by a factor of two. 相似文献
80.
Sergei D. Kirik Julia N. Zaitseva Igor S. Yakimov Nikolay N. Golovnev 《Acta Crystallographica. Section C, Structural Chemistry》2002,58(11):i159-i160
Lithium sodium aluminium fluoride was obtained as a white powder by melting a stoichiometric mixture of AlF3, NaF and LiF at 1223 K, and then cooling to 923 K and sintering at this temperature for 4 h. The ab initio crystal structure determination was carried out using X‐ray powder diffraction techniques. The monoclinic structure of LiNa2AlF6 can be related to cubic elpasolite. The Li and Al atoms lie on inversion centres. The main octahedral AlF6 structural elements are not deformed, but are rotated slightly with respect to the unit‐cell axes. The Li atoms have octahedral coordinations, whereas the Na atoms have cubo‐octahedral coordinations. The Na coordination polyhedron is distorted in comparison with that of elpasolite. 相似文献