全文获取类型
收费全文 | 471篇 |
免费 | 23篇 |
国内免费 | 4篇 |
专业分类
化学 | 371篇 |
力学 | 13篇 |
数学 | 61篇 |
物理学 | 53篇 |
出版年
2023年 | 2篇 |
2022年 | 18篇 |
2021年 | 6篇 |
2020年 | 9篇 |
2019年 | 4篇 |
2018年 | 13篇 |
2017年 | 4篇 |
2016年 | 19篇 |
2015年 | 21篇 |
2014年 | 18篇 |
2013年 | 23篇 |
2012年 | 25篇 |
2011年 | 25篇 |
2010年 | 14篇 |
2009年 | 15篇 |
2008年 | 34篇 |
2007年 | 26篇 |
2006年 | 24篇 |
2005年 | 24篇 |
2004年 | 31篇 |
2003年 | 16篇 |
2002年 | 24篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有498条查询结果,搜索用时 12 毫秒
1.
Functional Binding Surface of a β‐Hairpin VEGF Receptor Targeting Peptide Determined by NMR Spectroscopy in Living Cells
下载免费PDF全文
![点击此处可从《Chemistry (Weinheim an der Bergstrasse, Germany)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dr. Donatella Diana Anna Russomanno Dr. Lucia De Rosa Dr. Rossella Di Stasi Dr. Domenica Capasso Dr. Sonia Di Gaetano Dr. Alessandra Romanelli Dr. Luigi Russo Dr. Luca D. D'Andrea Prof. Roberto Fattorusso 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(1):91-95
In this study, the functional interaction of HPLW peptide with VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) was determined by using fast 15N‐edited NMR spectroscopic experiments. To this aim, 15N uniformly labelled HPLW has been added to Porcine Aortic Endothelial Cells. The acquisition of isotope‐edited NMR spectroscopic experiments, including 15N relaxation measurements, allowed a precise characterization of the in‐cell HPLW epitope recognized by VEGFR2. 相似文献
2.
Giuseppe Bartoli Sandra Giuli Enrico Marcantoni Massimo Massaccesi 《Tetrahedron letters》2006,47(37):6501-6504
The arylidene malonates with two different geminal carboxylate functions, a suitable class of substrates of several synthetic and pharmacological studies, are easily available through Knoevenagel condensation of ethyl tert-butyl malonate and different aromatic aldehydes. The results have increased the potentialities of CeCl3·7H2O-NaI system as a type of water-tolerant green Lewis acid promoter for carbon-carbon bond forming procedures. 相似文献
3.
Martinho M Banse F Bartoli JF Mattioli TA Battioni P Horner O Bourcier S Girerd JJ 《Inorganic chemistry》2005,44(25):9592-9596
The green complex S=1 [(TPEN)FeO]2+ [TPEN=N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine] has been obtained by treating the [(TPEN)Fe]2+ precursor with meta-chloroperoxybenzoic acid (m-CPBA). This high-valent complex belongs to the emerging family of synthetic models of Fe(IV)=O intermediates invoked during the catalytic cycle of biological systems. This complex exhibits spectroscopic characteristics that are similar to those of other models reported recently with a similar amine/pyridine environment. Thanks to its relative stability, vibrational data in solution have been obtained by Fourier transform infrared. A comparison of the Fe=O and Fe=(18)O wavenumbers reveals that the Fe-oxo vibration is not a pure one. The ability of the green complex to oxidize small organic molecules has been studied. Mixtures of oxygenated products derived from two- or four-electron oxidations are obtained. The reactivity of this [FeO]2+ complex is then not straightforward, and different mechanisms may be involved. 相似文献
4.
The title pyridazine 1 was found to react with both 2,3-dihydrofuran (2) and 3,4-dihydro-2H-pyran (9) to give the tetracyclic skeletons 5-8 and the phthalonitrile 12 through the intermediates 4 and 10, respectively. A more complex mechanism was ascertained for the reaction of 1 with the pyrroline 14 which, under suitable conditions, afforded the bicyclic derivative 19 as the predominant product; selective elaborations of this species into the 5,6-dicyanoindoles 22 and 23 are reported. 相似文献
5.
Tondi D Morandi F Bonnet R Costi MP Shoichet BK 《Journal of the American Chemical Society》2005,127(13):4632-4639
Bacterial expression of beta-lactamases is the most widespread resistance mechanism to beta-lactam antibiotics, such as penicillins and cephalosporins. There is a pressing need for novel, non-beta-lactam inhibitors of these enzymes. One previously discovered novel inhibitor of the beta-lactamase AmpC, compound 1, has several favorable properties: it is chemically dissimilar to beta-lactams and is a noncovalent, competitive inhibitor of the enzyme. However, at 26 microM its activity is modest. Using the X-ray structure of the AmpC/1 complex as a template, 14 analogues were designed and synthesized. The most active of these, compound 10, had a K(i) of 1 microM, 26-fold better than the lead. To understand the origins of this improved activity, the structures of AmpC in complex with compound 10 and an analogue, compound 11, were determined by X-ray crystallography to 1.97 and 1.96 A, respectively. Compound 10 was active in cell culture, reversing resistance to the third generation cephalosporin ceftazidime in bacterial pathogens expressing AmpC. In contrast to beta-lactam-based inhibitors clavulanate and cefoxitin, compound 10 did not up-regulate beta-lactamase expression in cell culture but simply inhibited the enzyme expressed by the resistant bacteria. Its escape from this resistance mechanism derives from its dissimilarity to beta-lactam antibiotics. 相似文献
6.
Bernardi A Potenza D Capelli AM García-Herrero A Cañada FJ Jiménez-Barbero J 《Chemistry (Weinheim an der Bergstrasse, Germany)》2002,8(20):4598-4612
As a step to delineate a strategy of ligand design for cholera toxin (CT), NMR studies were performed on several mimics of the GM1 ganglioside oligosaccharide. The conformation of these analogues was investigated first in solution and then upon binding to cholera toxin by transferred nuclear Overhauser effect (TR-NOE) measurements. It was demonstrated that CT selects a conformation similar to the global minima of the free saccharides from the ensemble of presented conformations. No evidence of major conformational distortions was obtained, but one or two of the available conformers of the hydroxyacid side chain appear to be selected in the bound state. The NMR data were interpreted with the aid of computer models, generated and analyzed by using a combination of different approaches (MacroModels' MC/EM and MC/SD, Autodock, and GRID). Analysis of the NMR data supported by computational studies allowed us to interpret the experimental observations and to derive workable models of the ligand:toxin complexes. These models suggest that the higher affinity of the (R)-lactic acid derivative 3 may stem from lipophilic interactions with a hydrophobic area in the toxin binding site located in the vicinity of the sialic acid side chain binding region of the CT:GM1 complex, and formed by the side chain of Ile-58 and Lys-34. Thus, the models obtained have allowed us to make useful design suggestions for the improvement of ligand affinity. 相似文献
7.
Massimo Lucarini Fabio Sciubba Donatella Capitani Maria Enrica Di Cocco Laura D’Evoli Alessandra Durazzo 《Natural product research》2020,34(1):53-62
AbstractThe study focuses on the understanding, at molecular level, the mechanism of interaction between protein and flavonoids. Collagen and catechin interactions were investigated by NMR in solution and solid state. The effect of catechin on the stability of collagen to oxidation was also explored. Collagen was treated with two concentrations of catechin solutions. Oxidation was carried out by incubation of collagen solution with three oxidation systems: Fe(II)/H2O2, Cu(II)/H2O2, and NaOCl/H2O2. The effects of oxidation systems were evaluated by high resolution 1?D and 2?D proton spectroscopy and solid state NMR (13C CP MAS) experiments. Interactions between collagen and catechin preferentially occur between catechin B ring and the amino acids Pro and Hyp of collagen. Results showed that both iron and copper oxidation systems were able to interact with collagen by site specific attack. Moreover, catechin protects collagen proline from oxidation by metal/H2O2 systems, preventing copper and iron approach to collagene molecule;this behaviour was more evident for the copper/H2O2 system. 相似文献
8.
Fabbrizzi L Foti F Licchelli M Maccarini PM Sacchi D Zema M 《Chemistry (Weinheim an der Bergstrasse, Germany)》2002,8(21):4965-4972
A cyclam-like macrocycle has been synthesized with a pendant arm containing a dansylamide group. In the corresponding nickel(II) complex, binding of the pendant arm to the metal is pH controlled. In particular, at pH 4.3, the sulfonamide group deprotonates and coordinates the NiII center, giving rise to a complex of trigonal bipyramidal stereochemistry, as shown by X-ray diffraction studies performed on the crystalline complex salt. At pH 7.5, an OH- ion binds the metal and a six-coordinate species forms. The binding-detachment of the pendant arm to/from the NiII center is signaled by changes in the emission properties of the dansyl subunit in the side chain; the fluorescence of this side chain is high when the pendant arm is not coordinated and low when the sulfonamide group is bound to the metal. The system investigated represents the prototype of a light-emitting molecular machine, driven by a pH change. 相似文献
9.
[reaction: see text] A new mild method for protecting alcohols as t-butyl ethers is reported. The reaction proceeds with Mg(ClO4)2 and Boc2O and shows general applicability. The deprotection of t-butyl ethers has also been revisited. Preliminary results indicate the CeCl3 x 7H2O/NaI system is a very suitable catalyst for their removal. 相似文献
10.