全文获取类型
收费全文 | 161篇 |
免费 | 1篇 |
专业分类
化学 | 98篇 |
晶体学 | 6篇 |
力学 | 2篇 |
数学 | 6篇 |
物理学 | 50篇 |
出版年
2021年 | 1篇 |
2019年 | 1篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2013年 | 6篇 |
2012年 | 4篇 |
2011年 | 6篇 |
2010年 | 6篇 |
2009年 | 3篇 |
2008年 | 8篇 |
2007年 | 15篇 |
2006年 | 15篇 |
2005年 | 4篇 |
2004年 | 6篇 |
2003年 | 5篇 |
2002年 | 10篇 |
2001年 | 9篇 |
2000年 | 3篇 |
1999年 | 9篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 7篇 |
1991年 | 2篇 |
1989年 | 2篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1975年 | 3篇 |
1969年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有162条查询结果,搜索用时 0 毫秒
1.
2.
RNA targeting is an exciting frontier for drug design. Intriguing targets include functional RNA structures in structurally-conserved untranslated regions (UTRs) of many lethal viruses. However, computational docking screens, valuable in protein structure targeting, fail for inherently flexible RNA. Herein we harness MD simulations with Markov state modeling to enable nanosize metallo-supramolecular cylinders to explore the dynamic RNA conformational landscape of HIV-1 TAR untranslated region RNA (representative for many viruses) replicating experimental observations. These cylinders are exciting as they have unprecedented nucleic acid binding and are the first supramolecular helicates shown to have anti-viral activity in cellulo: the approach developed in this study provides additional new insight about how such viral UTR structures might be targeted with the cylinder binding into the heart of an RNA-bulge cavity, how that reduces the conformational flexibility of the RNA and molecular details of the insertion mechanism. The approach and understanding developed represents a new roadmap for design of supramolecular drugs to target RNA structural motifs across biology and nucleic acid nanoscience.MD simulations and Markov state modeling explore induced fit binding of metallo-helicates to bulges in dynamic TAR RNA, reproduce experimental data, show how RNA conformational flexibility is reduced, and give mechanistic insight into insertion. 相似文献
3.
4.
5.
An animal model of solar-aged skin: histological, physical, and visible changes in UV-irradiated hairless mouse skin 总被引:8,自引:0,他引:8
Albino hairless mice (Skh:HR-l) exposed to sub-erythemal doses of UVB or UVA radiation display physical, visible, and histological alterations. Skin surface replicas, transepidermal water loss, and skin fold thickness were found to change with irradiation. Visibly, the skin wrinkled with UVB and sagged with UVA exposure. These changes were graded on 3-point scales. Histological alterations included tissue thickening, loss of elastic fibers, elastosis, loss of collagen, and increases in muco-substances. The UVB alterations occur to a much lesser extent with an SPF-15 (7% PABA and 3% oxybenzone) sunscreen product. This sunscreen product had little effect on development of UVA-induced changes. However, an efficient UVA sunscreen (Parsol 1789) did reduce the UVA-induced changes. Many of the UVB-induced alterations regressed after UVB irradiation was stopped. No regression in UVA-induced alterations was observed when UVA irradiation was stopped. Qualitatively, the effects with UVA irradiation were like those observed in mouse chronological aging. These models and the convenient physical and visible grading methods described can be used to determine the effectiveness of topical treatments, such as sunscreens. 相似文献
6.
7.
8.
Targeted cellular delivery of drugs to specific tissues is an important goal in biomedical chemistry. Achieving this requires harnessing and applying molecular-level recognition events prevalent in (or specific to) the desired tissue type. Tissues rich in estrogen receptors (ERs), which include many types of breast cancer, accumulate molecules that have high binding affinities for these receptors. Therefore, molecules that (i) bind to the ER, (ii) have favorable cellular transport properties, and (iii) contain a second functionality (such as a center that may be used for diagnostic imaging or medical therapy) are exciting synthetic targets in the field of drug delivery. To this end, we have prepared a range of metallo-estrogens based on 17alpha-ethynylestradiol and examined their binding to the ER both as isolated receptor and in whole cell assays (ER positive MCF-7 cells). Estrogens functionalized with metal binding units are prepared by palladium-catalyzed cross-coupling reactions and a wide range of metal centers introduced readily. All the compounds prepared and tested exhibit effective binding to the estrogen receptor and are delivered across the cell membrane into MCF-7 cells. In the whole cell assays, despite their monocationic nature, the palladium and platinum complexes prepared exhibit similar (and even enhanced) receptor binding affinities compared to their corresponding neutral free ligands. It is unprecedented for a higher ER binding affinity to be observed for a cationic complex than for its metal-free ligand. 相似文献
9.
Malina J Hannon MJ Brabec V 《Chemistry (Weinheim an der Bergstrasse, Germany)》2008,14(33):10408-10414
Metallosupramolecular chemistry was used to design a new class of synthetic agents, namely, tetracationic supramolecular cylinders, that bind strongly and noncovalently in the major groove of DNA. To gain additional information on interactions of the cylinders with DNA we explored DNA unwinding and sequence-specific binding properties, as well as DNA photonuclease activity of ruthenium(II) metallosupramolecular cylinder [Ru(2)L(3)](4+), where L is a bis-pyridylimine ligand. We found that [Ru(2)L(3)](4+) unwinds negatively supercoiled plasmid DNA and exhibits binding preference to regular alternating purine-pyrimidine sequences in a similar way to the [Fe(2)L(3)](4+) analogue. Photocleavage studies showed that, unlike [Fe(2)L(3)](4+), [Ru(2)L(3)](4+) induces single-strand breaks on irradiation by visible and UVA light and cleaves DNA mainly at guanine residues contained preferentially in regularly alternating purine-pyrimidine nucleotides. As [Ru(2)L(3)](4+) binds and cleaves DNA in a sequence-dependent manner, it may provide a useful tool for basic and applied biology, such as for controlled manipulation of the genome. 相似文献
10.