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排序方式: 共有216条查询结果,搜索用时 15 毫秒
211.
Galina F. Makhaeva Nadezhda V. Kovaleva Elena V. Rudakova Natalia P. Boltneva Sofya V. Lushchekina Irina I. Faingold Darya A. Poletaeva Yuliya V. Soldatova Raisa A. Kotelnikova Igor V. Serkov Anatoly K. Ustinov Alexey N. Proshin Eugene V. Radchenko Vladimir A. Palyulin Rudy J. Richardson 《Molecules (Basel, Switzerland)》2020,25(24)
New hybrids of 4-amino-2,3-polymethylenequinoline with different sizes of the aliphatic ring linked to butylated hydroxytoluene (BHT) by enaminoalkyl (7) or aminoalkyl (8) spacers were synthesized as potential multifunctional agents for Alzheimer’s disease (AD) treatment. All compounds were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. Lead compound 8c, 2,6-di-tert-butyl-4-{[2-(7,8,9,10- tetrahydro-6H-cyclohepta[b]quinolin-11-ylamino)-ethylimino]-methyl}-phenol exhibited an IC50(AChE) = 1.90 ± 0.16 µM, IC50(BChE) = 0.084 ± 0.008 µM, and 13.6 ± 1.2% propidium displacement at 20 μM. Compounds possessed low activity against carboxylesterase, indicating likely absence of clinically unwanted drug-drug interactions. Kinetics were consistent with mixed-type reversible inhibition of both cholinesterases. Docking indicated binding to catalytic and peripheral AChE sites; peripheral site binding along with propidium displacement suggest the potential of the hybrids to block AChE-induced β-amyloid aggregation, a disease-modifying effect. Compounds demonstrated high antioxidant activity in ABTS and FRAP assays as well as inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Conjugates 8 with amine-containing spacers were better antioxidants than those with enamine spacers 7. Computational ADMET profiles for all compounds predicted good blood-brain barrier distribution (permeability), good intestinal absorption, and medium cardiac toxicity risk. Overall, based on their favorable pharmacological and ADMET profiles, conjugates 8 appear promising as candidates for AD therapeutics. 相似文献
212.
Elinson Michail N. Ryzhkova Yuliya E. Krymov Stepan K. Vereshchagin Anatoly N. Goloveshkin Alexander S. Egorov Mikhail P. 《Monatshefte für Chemie / Chemical Monthly》2020,151(4):567-573
Monatshefte für Chemie - Chemical Monthly - The new electrochemically induced multicomponent assembling was found: the electrocatalytic transformation of benzaldehydes,... 相似文献
213.
The last decade has seen a steady increase in screening of cDNA expression product libraries displayed on the surface of filamentous bacteriophage. At the same time, the range of applications extended from the identification of novel allergens over disease markers to protein-protein interaction studies. However, the generation and selection of cDNA phage display libraries is subjected to intrinsic biological limitations due to their complex nature and heterogeneity, as well as technical difficulties regarding protein presentation on the phage surface. Here, we review the latest developments in this field, discuss a number of strategies and improvements anticipated to overcome these challenges making cDNA and open reading frame (ORF) libraries more readily accessible for phage display. Furthermore, future trends combining phage display with next generation sequencing (NGS) will be presented. 相似文献
214.
Konovalova IS Nelyubina YV Lyssenko KA Paponov BV Shishkin OV 《The journal of physical chemistry. A》2011,115(30):8550-8562
In this paper intra- and intermolecular interactions in crystals of 3,4-diamino-1,2,4-triazole (DAT) and its 5-methyl derivative (DAMT) were investigated in details by experimental (high-resolution X-ray diffraction) and theoretical (ab initio quantum chemistry (MP2/aug-cc-pvdz), AIM, and NBO) methods. Influence of n-π conjugation and n→σ* hyperconjugation on the geometry of DAT and DAMT molecules was shown. All intermolecular interactions in crystals of the DAT and DAMT including weak X-H···π and mixed X-H···N/X-H···π hydrogen bonds were considered. Comparison of BCP characteristics of these interactions from experimental and theoretical charge density distribution demonstrates systematic increase of bonding in isolated dimers compared with dimers in the crystal phase. The ability of amino groups in both crystals serve as proton acceptors in hydrogen bonding was confirmed. 相似文献
215.
Mei Y Frederickson CJ Giblin LJ Weiss JH Medvedeva Y Bentley PA 《Chemical communications (Cambridge, England)》2011,47(25):7107-7109
A new class of in vitro Zn(II) chemosensor based on dipyrrin has been developed. 5-(Pyren-1-yl)-4,6-dipyrrin (PYDPY1) was synthesized and exhibited high selectivity and sensitivity to Zn(II) (K(d) of 20 μM) compared to other metal ions. PYDPY1 was applied to the visualization of Zn(II) concentration in hippocampal tissue. 相似文献
216.
In this paper we give necessary and sufficient conditions for the system of positive numbers Mk1,Mk2,…,Mkd, 0≤k1<…<kd≤r, to guarantee the existence of an r -monotone function defined on the negative half-line R− and such that ‖x(ki)‖∞=Mki, i=1,2,…,d. We also discuss some applications of the obtained results and connections with other problems. 相似文献