全文获取类型
收费全文 | 25983篇 |
免费 | 854篇 |
国内免费 | 144篇 |
专业分类
化学 | 18677篇 |
晶体学 | 216篇 |
力学 | 491篇 |
数学 | 3281篇 |
物理学 | 4316篇 |
出版年
2023年 | 182篇 |
2022年 | 266篇 |
2021年 | 363篇 |
2020年 | 485篇 |
2019年 | 470篇 |
2018年 | 315篇 |
2017年 | 272篇 |
2016年 | 730篇 |
2015年 | 624篇 |
2014年 | 746篇 |
2013年 | 1225篇 |
2012年 | 1616篇 |
2011年 | 1789篇 |
2010年 | 1033篇 |
2009年 | 868篇 |
2008年 | 1487篇 |
2007年 | 1407篇 |
2006年 | 1392篇 |
2005年 | 1296篇 |
2004年 | 1134篇 |
2003年 | 856篇 |
2002年 | 896篇 |
2001年 | 437篇 |
2000年 | 369篇 |
1999年 | 370篇 |
1998年 | 362篇 |
1997年 | 341篇 |
1996年 | 349篇 |
1995年 | 291篇 |
1994年 | 319篇 |
1993年 | 299篇 |
1992年 | 265篇 |
1991年 | 192篇 |
1990年 | 218篇 |
1989年 | 185篇 |
1988年 | 197篇 |
1987年 | 173篇 |
1986年 | 163篇 |
1985年 | 274篇 |
1984年 | 258篇 |
1983年 | 183篇 |
1982年 | 200篇 |
1981年 | 185篇 |
1980年 | 182篇 |
1979年 | 164篇 |
1978年 | 195篇 |
1977年 | 180篇 |
1976年 | 137篇 |
1975年 | 132篇 |
1974年 | 157篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Smith JT Tomfohr JK Wells MC Beebe TP Kepler TB Reichert WM 《Langmuir : the ACS journal of surfaces and colloids》2004,20(19):8279-8286
A novel technique for the quantitative observation of cell migration along linear gradient substrates functionalized with adhesive proteins is presented. Gradients of the cell adhesion molecule fibronectin are generated by the cross diffusion of functionalizable alkanethiols on gold and characterized by X-ray photoelectron spectroscopy and surface plasmon resonance. Two distinct migration assays are described that characterize the movement of either sparsely populated noncontacting cells or a confluent monolayer of cells into free space. The drift speed of bovine aortic endothelial cells is measured and shown to increase along a fibronectin gradient when compared to a uniform control substrate using both assays. The results of these experiments establish reproducible conditions for studies of cell migration on gradients of surface-bound ligands. 相似文献
992.
We have prepared glucose and cellobiose conjugates at the phenolic 3- and hydroxylic 17-positions of the pure anti-estrogenic compound fulvestrant (ICI 182,780), which has recently been approved in the USA for the treatment of advanced postmenopausal breast cancer. Glycosylation at the 17-position was achieved most effectively using pivaloyl protection of the sugar imidates employed, which we found suppressed the competing transacylation reaction and led to improved yields of the product glycosides. 相似文献
993.
Frank Seela KhalilI. Shaikh Thomas Wiglenda Peter Leonard 《Helvetica chimica acta》2004,87(10):2507-2516
The syntheses of N7‐glycosylated 9‐deazaguanine 1a as well as of its 9‐bromo and 9‐iodo derivatives 1b , c are described. The regioselective 9‐halogenation with N‐bromosuccinimide (NBS) and N‐iodosuccinimide (NIS) was accomplished at the protected nucleobase 4a (2‐{[(dimethylamino)methylidene]amino}‐3,5‐dihydro‐3‐[(pivaloyloxy)methyl]‐4H‐pyrrolo[3,2‐d]pyrimidin‐4‐one). Nucleobase‐anion glycosylation of 4a – c with 2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D ‐erythro‐pentofuranosyl chloride ( 5 ) furnished the fully protected intermediates 6a – c (Scheme 2). They were deprotected with 0.01M NaOMe yielding the sugar‐deprotected derivatives 8a – c (Scheme 3). At higher concentrations (0.1M NaOMe), also the pivaloyloxymethyl group was removed to give 7a – c , while conc. aq. NH3 solution furnished the nucleosides 1a – c . In D2O, the sugar conformation was always biased towards S (67–61%). 相似文献
994.
Dr. Nadja A. Simeth Thomas Kinateder Dr. Chitra Rajendran Julian Nazet Prof. Dr. Rainer Merkl Prof. Dr. Reinhard Sterner Prof. Dr. Burkhard König Dr. Andrea C. Kneuttinger 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(7):2439-2451
Light regulation of drug molecules has gained growing interest in biochemical and pharmacological research in recent years. In addition, a serious need for novel molecular targets of antibiotics has emerged presently. Herein, the development of a photocontrollable, azobenzene-based antibiotic precursor towards tryptophan synthase (TS), an essential metabolic multienzyme complex in bacteria, is presented. The compound exhibited moderately strong inhibition of TS in its E configuration and five times lower inhibition strength in its Z configuration. A combination of biochemical, crystallographic, and computational analyses was used to characterize the inhibition mode of this compound. Remarkably, binding of the inhibitor to a hitherto-unconsidered cavity results in an unproductive conformation of TS leading to noncompetitive inhibition of tryptophan production. In conclusion, we created a promising lead compound for combatting bacterial diseases, which targets an essential metabolic enzyme, and whose inhibition strength can be controlled with light. 相似文献
995.
Johan F. A. Pijnenborg Eline A. Visser Dr. Marek Noga Emiel Rossing Raisa Veizaj Prof. Dirk J. Lefeber Dr. Christian Büll Dr. Thomas J. Boltje 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(12):4022-4027
Fucosylation of glycans impacts a myriad of physiological and pathological processes. Inhibition of fucose expression emerges as a potential therapeutic avenue for example in cancer, inflammation, and infection. In this study, we found that protected 2-fluorofucose 1-phosphate efficiently inhibits cellular fucosylation with a four to seven times higher potency than known inhibitor 2FF, independently of the anomeric stereochemistry. Nucleotide sugar analysis revealed that both the α- and β-GDP-2FF anomers are formed inside the cell. In conclusion, we developed A2FF1P and B2FF1P as potent new tools for studying the role of fucosylation in health and disease and they are potential therapeutic candidates. 相似文献
996.
Thomas D. Hettich Richard Rudolf Dr. Christoph M. Feil Nicholas Birchall Dr. Martin Nieger Prof. Dr. Dr. h. c. Dietrich Gudat 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(17):5412-5416
Unprecedented metalated phosphonite boranes were prepared from PH-substituted precursors and silyl amides. Although potassium derivatives were thermally stable and could even be isolated and structurally characterised, lithiated analogues proved to be unstable towards self-condensation under cleavage of LiOR at ambient temperature. Reaction studies revealed that the metalated phosphonite boranes exhibit ambiphilic character. Their synthetic potential as nucleophilic building blocks was demonstrated in the synthesis of the first stannylated phosphonite representing a new structural motif in phosphine chemistry. 相似文献
997.
Shortridge MD Triplet T Revesz P Griep MA Powers R 《Computational Biology and Chemistry》2011,35(1):24-33
Protein sequence space is vast compared to protein fold space. This raises important questions about how structures adapt to evolutionary changes in protein sequences. A growing trend is to regard protein fold space as a continuum rather than a series of discrete structures. From this perspective, homologous protein structures within the same functional classification should reveal a constant rate of structural drift relative to sequence changes. The clusters of orthologous groups (COG) classification system was used to annotate homologous bacterial protein structures in the Protein Data Bank (PDB). The structures and sequences of proteins within each COG were compared against each other to establish their relatedness. As expected, the analysis demonstrates a sharp structural divergence between the bacterial phyla Firmicutes and Proteobacteria. Additionally, each COG had a distinct sequence/structure relationship, indicating that different evolutionary pressures affect the degree of structural divergence. However, our analysis also shows the relative drift rate between sequence identity and structure divergence remains constant. 相似文献
998.
Thomas Huber Andrew E. Torda Wilfred F. van Gunsteren 《Journal of computer-aided molecular design》1994,8(6):695-708
Summary The concept of memory has been introduced into a molecular dynamics algorithm. This was done so as to persuade a molecular system to visit new areas of conformational space rather than be confined to a small number of low-energy regions. The method is demonstrated on a simple model system and the 11-residue cyclic peptide cyclosporin A. For comparison, calculations were also performed using simulated temperature annealing and a potential energy annealing scheme. Although the method can only be applied to systems with a small number of degrees of freedom, it offers the chance to generate a multitude of different low-energy structures, where other methods only give a single one or few. This is clearly important in problems such as drug design, where one is interested in the conformational spread of a system. 相似文献
999.
For a permanently manned outpost on the moon – a moon village – a first holistic concept of a sustainable material flow has been established. From this context three dedicated topics have been investigated to more depth: Additive manufacturing (AM) of Al from disused space crafts, AM of structural elements with local resources, and resource extraction from regolith via thermal processes. 相似文献
1000.
We have prepared a range of well-defined copolymers of styrene and L-proline functionalized styrene (5-11 kDa) using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques and explored their use in supported catalysis. Upon deprotection of the L-proline functionalities, the solution self-assembly of these copolymers was investigated in mixed solvent systems. The resulting assemblies were characterized by dynamic light scattering, transmission electron microscopy (on graphene oxide substrates, along with cryo-TEM and tomography), and scanning electron microscopy. The application of these functional assemblies as supported catalysts for the aldol condensation reaction was explored using cyclohexanone and 4-nitrobenzaldehyde. The rate and selectivity of solution catalysis in our self-assembled system were comparable to those of L-proline, and a significant advantage of our system was that the polymer support could be utilized at lower catalyst loadings with comparable activity and also could be recycled a number of times while maintaining activity and selectivity. 相似文献