全文获取类型
收费全文 | 345篇 |
免费 | 18篇 |
国内免费 | 1篇 |
专业分类
化学 | 245篇 |
晶体学 | 1篇 |
力学 | 8篇 |
数学 | 64篇 |
物理学 | 46篇 |
出版年
2023年 | 1篇 |
2022年 | 6篇 |
2021年 | 2篇 |
2020年 | 9篇 |
2019年 | 8篇 |
2018年 | 9篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 6篇 |
2014年 | 16篇 |
2013年 | 19篇 |
2012年 | 26篇 |
2011年 | 37篇 |
2010年 | 14篇 |
2009年 | 13篇 |
2008年 | 29篇 |
2007年 | 33篇 |
2006年 | 30篇 |
2005年 | 18篇 |
2004年 | 19篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有364条查询结果,搜索用时 31 毫秒
361.
Ordered assembly of collagen molecules on flat substrates has potential for various applications and serves as a model system for studying the assembly process. While previous studies demonstrated self-assembly of collagen on muscovite mica into highly ordered layers, the mechanism by which different conditions affect the resulting morphology remains to be elucidated. Using atomic force microscopy, we follow the assembly of collagen on muscovite mica at a concentration lower than the critical fibrillogenesis concentration in bulk. Initially, individual collagen molecules adsorb to mica and subsequently nucleate into fibrils possessing the 67 nm D-periodic bands. Emergence of fibrils aligned in parallel despite large interfibril distances agrees with an alignment mechanism guided by the underlying mica. The epitaxial growth was further confirmed by the formation of novel triangular networks of collagen fibrils on phlogopite mica, whose surface lattice is known to have a hexagonal symmetry, whereas the more widely used muscovite does not. Comparing collagen assembly on the two types of mica at different potassium concentrations revealed that potassium binds to the negatively charged mica surface and neutralizes it, thereby reducing the binding affinity of collagen and enhancing surface diffusion. These results suggest that collagen assembly on mica follows the surface adsorption, diffusion, nucleation, and growth pathway, where the growth direction is determined at the nucleation step. Comparison with other molecules that assemble similarly on mica supports generality of the proposed assembly mechanism, the knowledge of which will be useful for controlling the resulting surface morphologies. 相似文献
362.
Stephen J. ButlerKatrina A. Jolliffe Wee Yu Gladys LeeMatthew J. McDonough Aaron J. Reynolds 《Tetrahedron》2011,67(5):1019-1029
Three analogues of the Lissoclinum class of cyclic peptides, bearing dipicolylamino functionalised side chains, have been synthesised using a stepwise approach followed by macrocyclisation. Attempts to incorporate dipicolylamino functionalised side chains prior to peptide synthesis resulted in epimerisation, but this was overcome by functionalising the ornithine side chains with dipicolylamino groups after the macrocyclisation reaction. 相似文献
363.
Both metal complexes and organic molecules are widely used for the treatment of various diseases including cancer - in addition to surgery and radiotherapy. Recent years have witnessed a surge of interest in the application of organometallic compounds to treat cancer and other diseases. Indeed, the unique properties of organometallic compounds, intermediate between those of classical inorganic and organic materials provide new opportunities in medicinal chemistry. In this review, based on the award lecture at ICBOMC’10, we describe a class of ruthenium(II)-arene complexes that are weakly cytotoxic in vitro, but show selective antimetastatic activity in vivo. These compounds, [Ru(η6-p-arene)Cl2(pta)] termed RAPTA, interact strongly with proteins, with the ability to discriminate binding to different proteins, but show a relatively low propensity to bind DNA, which is considered to be the main target of many metal-based drugs. The basic RAPTA structure is quite stable in physiological environments, and studies have shown that aquation of the chloride bonds occurs, it may not be an essential step for anticancer drug activity - direct substitution with biomolecular targets is also possible. Based on the favorable physicochemical properties of RAPTA compounds, combined with their highly promising pharmacological properties, the structure represents an ideal scaffold for rational drug design. Thus far, strategies to overcome drug resistance, by interference with critical enzymes responsible for drug deactivation, and tumor targeting, by tethering to human serum albumin via hydrolyzable linkers, have been demonstrated. However, many more approaches can be envisaged. In any case, the net result are a type of hybrid compounds, that occupy a niche somewhere between classical cisplatin-type anticancer agents that are widely applied to many tumor types and targeted therapies based on organic structures used to inhibit specific enzymes. As such, should these compounds prove themselves in the clinic it is not inconceivable that they could be rapidly refined to form personalized chemotherapies. 相似文献
364.
Parker LJ Italiano LC Morton CJ Hancock NC Ascher DB Aitken JB Harris HH Campomanes P Rothlisberger U De Luca A Lo Bello M Ang WH Dyson PJ Parker MW 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(28):7806-7816
Platinum-based cancer drugs, such as cisplatin, are highly effective chemotherapeutic agents used extensively for the treatment of solid tumors. However, their effectiveness is limited by drug resistance, which, in some cancers, has been associated with an overexpression of pi class glutathione S-transferase (GST P1-1), an important enzyme in the mercapturic acid detoxification pathway. Ethacraplatin (EA-CPT), a trans-Pt(IV) carboxylate complex containing ethacrynate ligands, was designed as a platinum cancer metallodrug that could also target cytosolic GST enzymes. We previously reported that EA-CPT was an excellent inhibitor of GST activity in live mammalian cells compared to either cisplatin or ethacrynic acid. In order to understand the nature of the drug-protein interactions between EA-CPT and GST P1-1, and to obtain mechanistic insights at a molecular level, structural and biochemical investigations were carried out, supported by molecular modeling analysis using quantum mechanical/molecular mechanical methods. The results suggest that EA-CPT preferentially docks at the dimer interface at GST P1-1 and subsequent interaction with the enzyme resulted in docking of the ethacrynate ligands at both active sites (in the H-sites), with the Pt moiety remaining bound at the dimer interface. The activation of the inhibitor by its target enzyme and covalent binding accounts for the strong and irreversible inhibition of enzymatic activity by the platinum complex. 相似文献