全文获取类型
收费全文 | 103篇 |
免费 | 17篇 |
出版年
2023年 | 2篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2018年 | 1篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2014年 | 5篇 |
2013年 | 9篇 |
2012年 | 4篇 |
2011年 | 2篇 |
2010年 | 1篇 |
2009年 | 3篇 |
2008年 | 7篇 |
2007年 | 2篇 |
2006年 | 5篇 |
2005年 | 5篇 |
2004年 | 1篇 |
2003年 | 8篇 |
2002年 | 5篇 |
2001年 | 5篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1977年 | 3篇 |
1974年 | 1篇 |
排序方式: 共有120条查询结果,搜索用时 15 毫秒
51.
52.
Quinoline alkaloids are abundant in the Rutaceae, and many have exhibited cytotoxic activity. Because structurally related
antitumor alkaloids such as camptothecin and fagaronine are known to function as intercalative topoisomerase poisons, it is
hypothesized that cytotoxic Stauranthus alkaloids may also serve as intercalative topoisomerase inhibitors. To test this hypothesis theoretically, ten Stauranthus quinoline alkaloids were examined for potential intercalation into DNA using a molecular docking approach. Four of the alkaloids
(stauranthine, skimmianine, 3′,6′-dihydroxy-3′,6′-dihydrostauranthine, and trans-3′,4′-dihydroxy-3′,4′-dihydrostauranthine) were able to intercalatively dock consistently into DNA. In order to probe the
intermolecular interactions that may be responsible for intercalation of these quinoline alkaloids, density functional calculations
have been carried out using both the B3LYP and M06 functionals. M06 calculations indicated favorable π–π interactions between
either skimmianine or stauranthine and the guanine–cytosine base pair. Furthermore, the lowest-energy face-to-face orientation
of stauranthine with guanine is consistent with favorable dipole–dipole orientations, favorable electrostatic interactions,
and favorable frontier molecular orbital interactions. Likewise, the lowest-energy face-to-face orientation of stauranthine
with the guanine–cytosine base pair reveals favorable electrostatic interactions as well as frontier molecular orbital interactions.
Thus, not only can quinoline alkaloids dock intercalatively into DNA, but the docked orientations are also electronically
favorable.
相似文献
53.
RW Dapson 《Biotechnic & histochemistry》2013,88(3):133-140
Although the mechanics of formalin fixation and antigen retrieval have been studied extensively and reviewed periodically, little attention has been directed toward conformational changes in target molecules. Formaldehyde changes the shape of tissue molecules by appending small hydroxymethyl groups to them. These adducts, in turn, can react with other tissue molecules to form crosslinks, or they can participate in a variety of reactions during tissue processing, including formation of imines, ethoxymethyl adducts, and further crosslinks. Under the influence of alcohol dehydration, fixed DNA may fragment and form a variety of depurination products. The situation becomes even more complex with short fixation times because under these conditions, the dehydrating agent used for tissue processing denatures macromolecules in other ways, most notably through rearrangement of molecular shape to move hydrophobic realms outward and hydrophilic areas inward (hydrophobic inversions). How tissue molecules are modified affects the outcome of immunohistochemical staining and prospects for restoration of antigenicity. Immunoreacitivity may be compromised because epitopes are either sterically hidden, but otherwise unaffected, or they have been altered more directly. Enzyme-based retrieval methods are best suited for the former because they literally snip the molecule apart to reveal the portions of interest. Heat-induced retrieval with buffers can demodify affected epitopes by removing adducts and breaking crosslinks. The choice of temperature and pH is usually critical for optimal retrieval. Effective temperatures are directly related to the strength of bonds-higher temperatures are needed to break stronger bonds. The pH of the retrieval solution determines the charge on the tissue molecule; the goal is to create a charge that causes the demodified molecule to assume a near natural conformation. Rational use of these concepts should lead to better control of immunohistochemical reactions. 相似文献
54.
In June 2008, the Biological Stain Commission sponsored A Seminar on Dyes and Staining the purpose of which was twofold: first, to show that very useful information applicable to biomedical dyes and staining is available from unrelated disciplines and second, to summarize modern thinking on how dyes, solvents, and tissues interact to produce selective staining. In this introduction to the papers from the symposium, we acknowledge that biomedical dye research has declined as newer technologies have gained importance. We should point out, however, that dyes and staining still are vitally important. Moreover, needs abound for innovative studies concerned with dye analysis, synthesis, and mode of action. Concepts and tools from unrelated fields hold promise for significant breakthroughs in many areas of interest. 相似文献
55.
Background
Human African trypanosomiasis (HAT), a parasitic protozoal disease, is caused primarily by two subspecies of Trypanosoma brucei. HAT is a re-emerging disease and currently threatens millions of people in sub-Saharan Africa. Many affected people live in remote areas with limited access to health services and, therefore, rely on traditional herbal medicines for treatment.Methods
A molecular docking study has been carried out on phytochemical agents that have been previously isolated and characterized from Nigerian medicinal plants, either known to be used ethnopharmacologically to treat parasitic infections or known to have in-vitro antitrypanosomal activity. A total of 386 compounds from 19 species of medicinal plants were investigated using in-silico molecular docking with validated Trypanosoma brucei protein targets that were available from the Protein Data Bank (PDB): Adenosine kinase (TbAK), pteridine reductase 1 (TbPTR1), dihydrofolate reductase (TbDHFR), trypanothione reductase (TbTR), cathepsin B (TbCatB), heat shock protein 90 (TbHSP90), sterol 14α-demethylase (TbCYP51), nucleoside hydrolase (TbNH), triose phosphate isomerase (TbTIM), nucleoside 2-deoxyribosyltransferase (TbNDRT), UDP-galactose 4′ epimerase (TbUDPGE), and ornithine decarboxylase (TbODC).Results
This study revealed that triterpenoid and steroid ligands were largely selective for sterol 14α-demethylase; anthraquinones, xanthones, and berberine alkaloids docked strongly to pteridine reductase 1 (TbPTR1); chromenes, pyrazole and pyridine alkaloids preferred docking to triose phosphate isomerase (TbTIM); and numerous indole alkaloids showed notable docking energies with UDP-galactose 4′ epimerase (TbUDPGE). Polyphenolic compounds such as flavonoid gallates or flavonoid glycosides tended to be promiscuous docking agents, giving strong docking energies with most proteins.Conclusions
This in-silico molecular docking study has identified potential biomolecular targets of phytochemical components of antitrypanosomal plants and has determined which phytochemical classes and structural manifolds likely target trypanosomal enzymes. The results could provide the framework for synthetic modification of bioactive phytochemicals, de novo synthesis of structural motifs, and lead to further phytochemical investigations. 相似文献56.
Franklin Greif Harry S. Soroff R. Woodrow Setzer Lorne B. Taichman 《In vitro cellular & developmental biology. Plant》1988,24(10):985-989
Summary Epidermal keratinocytes grow in culture to form a stratified squamous epithelium. These cultures contain a replicating as
well as a terminally differentiating population and undergo surface desquamation. Epidermal growth factor (EGF) and cholera
toxin are usually employed as growth-promoting agents because they reduce the population doubling time; that is, the period
required to increase the total cell number twofold. There are three ways in which this reduction in population doubling time
could be achieved: (a) the time for one cell cycle or the cell cycle length may be shortened; (b) the number of cells that
withdraw from the cell cycle and terminally differentiate may be reduced; or (c) the number of cells that desquamate into
the medium over a set period of time may be reduced. We have explored these possibilities in growing cultures of epidermal
keratinocytes using a newly developed double-label assay. This assay gives a measure of both cell length and cell cycle withdrawal.
Results show that the growth enhancement induced by EGF and cholera toxin can be attributed primarily to a reduction in cell
cycle withdrawal and, to a lesser degree, to a reduction in cell cycle length. EGF and cholera toxin have no significant effect
on the rate of desquamation. A linear correlation was noted between cell cycle lengths and withdrawal, suggesting an interconnection
between the rate of cell renewal and the likelihood of undergoing terminal differentiation.
This research was supported by grant DE04511 from the National Institute of Dental Research, Bethesda, MD, and gifts from
the University Hospital Auxilliary, Health Sciences Center, SUNY Stony Brook, and the Suffolk County Volunteer Firefighter
Fund. 相似文献
57.
Background
Sequence related families of genes and proteins are common in bacterial genomes. In Escherichia coli they constitute over half of the genome. The presence of families and superfamilies of proteins suggest a history of gene duplication and divergence during evolution. Genome encoded protein families, their size and functional composition, reflect metabolic potentials of the organisms they are found in. Comparing protein families of different organisms give insight into functional differences and similarities. 相似文献58.
Joel A Dave Nico C Gey van Pittius Albert D Beyers Mario RW Ehlers Gordon D Brown 《BMC microbiology》2002,2(1):30
Background
Exported proteases are commonly associated with virulence in bacterial pathogens, yet there is a paucity of information regarding their role in Mycobacterium tuberculosis. There are five genes (mycP1-5) present within the genome of Mycobacterium tuberculosis H37Rv that encode a family of secreted, subtilisin-like serine proteases (the mycosins). The gene mycP1 (encoding mycosin-1) was found to be situated 3700 bp (four ORF's) from the RD1 deletion region in the genome of the attenuated vaccine strain M. bovis BCG (bacille de Calmette et Guérin) and was selected for further analyses due to the absence of expression in this organism. 相似文献59.
60.
Setzer MC Moriarity DM Lawton RO Setzer WN Gentry GA Haber WA 《Revista de biología tropical》2003,51(3-4):647-673
A pharmacological survey of plants from Monteverde, Costa Rica, including 165 species representing 61 families has been carried out. Crude plant extracts have been tested for in-vitro bactericidal and fungicidal activity as well as cytotoxic and anti-herpes activity. Of these, 123 extracts exhibited notable cytotoxicity, 62 showed antibacterial activity, 4 showed antifungal activity, and 8 showed promising antiviral activity. Thus, 101 of the plant species examined in this work, or 62%, showed marked bioactivity in one or more bioassays. These results underscore the phytomedicinal potential of Neotropical cloud forests. 相似文献