全文获取类型
收费全文 | 526篇 |
免费 | 29篇 |
专业分类
化学 | 415篇 |
晶体学 | 3篇 |
力学 | 10篇 |
数学 | 51篇 |
物理学 | 76篇 |
出版年
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 39篇 |
2020年 | 20篇 |
2019年 | 23篇 |
2018年 | 6篇 |
2017年 | 9篇 |
2016年 | 23篇 |
2015年 | 26篇 |
2014年 | 20篇 |
2013年 | 32篇 |
2012年 | 35篇 |
2011年 | 58篇 |
2010年 | 36篇 |
2009年 | 24篇 |
2008年 | 25篇 |
2007年 | 29篇 |
2006年 | 24篇 |
2005年 | 25篇 |
2004年 | 20篇 |
2003年 | 14篇 |
2002年 | 21篇 |
2001年 | 3篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
排序方式: 共有555条查询结果,搜索用时 812 毫秒
51.
Multitarget Drug Discovery for Alzheimer's Disease: Triazinones as BACE‐1 and GSK‐3β Inhibitors 下载免费PDF全文
Federica Prati Dr. Angela De Simone Dr. Paola Bisignano Dr. Andrea Armirotti Dr. Maria Summa Dr. Daniela Pizzirani Dr. Rita Scarpelli Dr. Daniel I. Perez Prof. Dr. Vincenza Andrisano Dr. Ana Perez‐Castillo Prof. Dr. Barbara Monti Francesca Massenzio Dr. Letizia Polito Prof. Dr. Marco Racchi Dr. Angelo D. Favia Dr. Giovanni Bottegoni Prof. Dr. Ana Martinez Prof. Dr. Maria Laura Bolognesi Prof. Dr. Andrea Cavalli 《Angewandte Chemie (International ed. in English)》2015,54(5):1578-1582
Cumulative evidence strongly supports that the amyloid and tau hypotheses are not mutually exclusive, but concomitantly contribute to neurodegeneration in Alzheimer′s disease (AD). Thus, the development of multitarget drugs which are involved in both pathways might represent a promising therapeutic strategy. Accordingly, reported here in is the discovery of 6‐amino‐4‐phenyl‐3,4‐dihydro‐1,3,5‐triazin‐2(1H)‐ones as the first class of molecules able to simultaneously modulate BACE‐1 and GSK‐3β. Notably, one triazinone showed well‐balanced in vitro potencies against the two enzymes (IC50 of (18.03±0.01) μM and (14.67±0.78) μM for BACE‐1 and GSK‐3β, respectively). In cell‐based assays, it displayed effective neuroprotective and neurogenic activities and no neurotoxicity. It also showed good brain permeability in a preliminary pharmacokinetic assessment in mice. Overall, triazinones might represent a promising starting point towards high quality lead compounds with an AD‐modifying potential. 相似文献
52.
Anahi Bucchini Donata Ricci Federica Messina Maria Carla Marcotullio Massimo Curini 《Natural product research》2015,29(12):1173-1176
The total phenolic content, antioxidant and antifungal activities of three Inula crithmoides extracts (n-hexane, methylene chloride and MeOH) were investigated. The methanolic extract showed the highest total phenolic content. In the DPPH assay, the methanolic and hexane extracts exhibited the highest DPPH-radical scavenging activity; in the 5-lipoxygenase assay, the hexane extract showed greater inhibitory effect with an IC50 similar to that of Trolox and ascorbic acid. The antifungal activity of the methanolic extract revealed a higher activity against Phytophtora cryptogea and Alternaria solani. 相似文献
53.
54.
Synthesis and Biological Evaluation of Several Dephosphonated Analogues of CMP‐Neu5Ac as Inhibitors of GM3‐Synthase 下载免费PDF全文
Dr. Paola Rota Dr. Federica Cirillo Dr. Marco Piccoli Dr. Antonio Gregorio Prof. Guido Tettamanti Prof. Pietro Allevi Prof. Luigi Anastasia 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(41):14614-14629
Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP‐Neu5Ac congeners and their anti ‐ GM3‐synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3‐synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade. 相似文献
55.
Malizia F Fait A Cruciani G 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(49):13892-13897
The crystal structures of three MgCl(2)·nEtOH complexes with n=1.5, 2.8, and 3.3 have been fully determined. Such complexes are the fundamental precursors for Ziegler-Natta polymerization catalysts used to produce polyolefins on a multimillion-ton scale worldwide. The ab initio structure solution showed that the structure of MgCl(2)·nEtOH complexes with n=1.5 and 2.8 are based on ribbons of metal-centered octahedra, whereas for n=3.3 this chainlike arrangement breaks into a threadlike structure of isolated octahedra linked by hydrogen bonds. A clear correlation between catalyst performance and the crystal structure of precursors has been found, and reveals the fundamental role of the latter in determining catalyst properties. The direct knowledge of building blocks in the precursor structures will help to develop more accurate models for activated catalysts. These models will not require the arbitrary and oversimplified assumption of locating the catalyst active sites on selected cut surfaces of the α-MgCl(2) crystal lattice. 相似文献
56.
Di Santo G Blankenburg S Castellarin-Cudia C Fanetti M Borghetti P Sangaletti L Floreano L Verdini A Magnano E Bondino F Pignedoli CA Nguyen MT Gaspari R Passerone D Goldoni A 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(51):14354-14359
Scratching the surface: Formation of a monolayer of 2H-tetraphenylporphyrins (2H-TPP) on Ag(111), either by sublimation of a multilayer in the range 525-600?K or by annealing (at the same temperature) a monolayer deposited at room temperature, induces a chemical modification of the molecules. Rotation of the phenyl rings into a flat conformation is observed and tentatively explained, by using DFT calculations, as a peculiar reaction due to molecular dehydrogenation. 相似文献
57.
Sala F Bagnati R Livi V Cereda R D'Incalci M Zucchetti M 《Journal of mass spectrometry : JMS》2011,46(10):1039-1045
E-3810, 6-[[7-[(1-aminocyclopropyl)methoxy]-6-methoxy-4-quinolyl]oxy]-N-methyl-naphthalene-1-carboxamide, is a novel, potent, dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors with antiangiogenic properties, now under early clinical evaluation as an anticancer agent. To investigate its clinical pharmacokinetics, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to measure the drug in human plasma on the basis of simple protein precipitation with methanol after addition of deuterated E-3810 as internal standard. The method requires a small volume of sample (100 μl) and is rapid and selective, allowing good resolution of peaks in 5 min. It is sensitive, precise, and accurate, with overall precision, expressed as CV%, always ≤7.1%, accuracy in the range 92.7%-104.4%, and high recovery, close to 100%. The limit of detection is 0.01 ng/ml, and the lower limit of quantitation is 2.0 ng/ml. The assay was validated in the range from the lower limit of quantitation up to 500.0 ng/ml. This is the first method developed and validated for analyzing E-3810 in human plasma. The method has been successfully applied to study E-3810 pharmacokinetics in cancer patients with solid tumors who are receiving daily oral doses of the drug during the phase I trial. 相似文献
58.
59.
Medana C Calza P Dal Bello F Raso E Minero C Baiocchi C 《Journal of mass spectrometry : JMS》2011,46(1):24-40
This paper deals with the photocatalytic transformation of N,N-diethyl-m-toluamide (DEET), one of the most widespread and efficient mosquito repellents, under simulated solar irradiation using titanium dioxide as the photocatalytic source of oxidizing species. The investigation involved monitoring of the DEET decomposition, the identification of intermediate compounds and the assessment of mineralization. High-resolution mass spectrometry was employed to assess the evolution of the photocatalyzed process over time. Fifty-one main species were identified after DEET transformation. Several isomeric species were formed and were characterized by analyzing MS and MS(n) spectra in full, and by comparison with parent molecule fragmentation pathways. In the DEET molecule, the initial transformation involved mono- and polyhydroxylation followed by oxidation of the alcohol groups, cleavage of the alkyl chains or ring opening. All these intermediates are easily degraded and DEET is completely mineralized after 4 h of irradiation. Microtox bioassay (Vibrio fischeri) was employed to evaluate the ecotoxicity of solutions treated by photocatalysis. 相似文献
60.
Menichini F Tundis R Bonesi M de Cindio B Loizzo MR Conforti F Statti GA Menabeni R Bettini R Menichini F 《Natural product research》2011,25(8):789-799
The chemical composition of the essential oil of Citrus medica L. cv. Diamante peel obtained by hydrodistillation, cold-pressing and supercritical carbon dioxide extraction techniques was determined by GC/MS analysis. Forty-six components were fully characterised. Limonene and γ-terpinene were the major components of the oils obtained by hydrodistillation (HD) and cold-pressing (CP), while citropten was the major constituent in the oil obtained by supercritical carbon dioxide extraction (SFE). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were evaluated. The essential oil obtained by hydrodistillation exerted the highest inhibitory activity against BChE (IC?? value of 154.6 μg mL?1) and AChE (IC?? value of 171.3 μg mL?1. Interestingly, the oil obtained by cold-pressing exhibited a selective inhibitory activity against AChE. The essential oils have also been evaluated for the inhibition of NO production in LPS induced RAW 264.7 macrophages. The oil obtained by hydrodistillation exerted a significant inhibition of NO production with an IC?? value of 17 μg mL?1 (IC?? of positive control 53 μg mL?1). 相似文献