全文获取类型
收费全文 | 195篇 |
免费 | 17篇 |
专业分类
212篇 |
出版年
2021年 | 2篇 |
2020年 | 2篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 7篇 |
2013年 | 7篇 |
2012年 | 13篇 |
2011年 | 6篇 |
2010年 | 8篇 |
2009年 | 2篇 |
2008年 | 6篇 |
2007年 | 6篇 |
2006年 | 8篇 |
2005年 | 5篇 |
2004年 | 12篇 |
2003年 | 3篇 |
2002年 | 10篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 9篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1964年 | 2篇 |
1961年 | 1篇 |
1954年 | 1篇 |
1938年 | 1篇 |
1936年 | 2篇 |
1935年 | 2篇 |
1932年 | 1篇 |
1927年 | 1篇 |
1909年 | 2篇 |
1904年 | 1篇 |
1881年 | 1篇 |
1865年 | 1篇 |
1864年 | 1篇 |
1863年 | 1篇 |
排序方式: 共有212条查询结果,搜索用时 15 毫秒
1.
This study demonstrated that agents capable of interacting with the minor groove in nuclear DNA interfere with topoisomerase II mediated effects of antitumor drugs such as VM-26 and m-AMSA. Distamycin, Hoechst 33258, and DAPI were used as agents capable of AT-specific binding in the minor groove of DNA while producing no profound long-range distortion of DNA structure. In intact nuclei from L1210 cells, these minor groove binders inhibited the induction of topoisomerase II mediated DNA damage (DNA-protein cross-links and DNA double-strand breaks) by VM-26 and m-AMSA. The inhibitory effects of distamycin reflected prevention of formation of new lesions but not reversal of preexisting damage. The minor groove binders did not differentiate between lesions induced by an intercalator, m-AMSA, or by a DNA-nonbinding drug, VM-26. All three groove binders inhibited DNA breaks more strongly than DNA-protein cross-links. The inhibitory potency correlated with the size of minor groove binders and the size of their DNA-binding sites: distamycin (5 bp) greater than Hoechst 33258 (4 bp) greater than DAPI (3 bp). The results showed that DNA minor groove binders are a new type of modulators of the action of topoisomerase II targeted drugs. 相似文献
2.
Summary The photoreceptor microvilli of some nocturnal spiders (Isopeda andOlios in theSparassidae, andClubiona in theClubionidae) are wide (80–140 nm), and microvilli from adjacent receptors are interdigitated. Because microvillar diameters are relatively large in relation to the thicknesses of thin sections, it is possible to examine cytoskeletal structures closely associated with the microvillar plasmalemmae directly.Retinae were treated with a specific inhibitor of cysteine proteases before primary fixation for electron microscopy in a Ca2+-chelating medium. Cytoskeletal components were stabilized with tannic acid. A variety of microvillar profiles was obtained, consistent with an assumption that they represent imperfect preservation of anin vivo plasmalemmal undercoat, inferred to consist of longitudinally-disposed microfilaments, presumptively bonded to the microvillar plasmalemma. The microvillar lumen is inferred to be empty of cytoskeletal components in life.This model is discussed in terms of 1. the cytoskeletal organisation of microvilli of the primitive photoreceptors of a leech (Blest
et al. 1983), where the arrangement of microfilaments resembles that in the vertebrate intestinal brush-border; 2. the large complement of membrane-associated oligomeric actin in rhabdoms of crayfish, where identifiable microfilaments cannot be resolved within microvilli by transmission electron microscopy (de Couet
et al. 1984), and a single visualizable axial filament of uncertain composition is linked to the plasmalemma by side-arms. 相似文献
3.
4.
Independently of their agonistic or antagonistic activity on different isolated tissue preparations, the kinin analogues investigated induce histamine release on rat peritoneal mast cells. The effectivity of most compounds is 10 to 100 times higher than that of bradykinin. Beside the positively charged amino acids, the elongation at the N-terminus with hydrophobic amino acids and the replacement of amino acids in the bradykinin sequence (especially at position 7) with aromatic residues is important for a high histamine-releasing activity. 相似文献
5.
We consider two-state automata playing repeatedly the Prisoner's Dilemma (or any other 2 × 2-game). The 16 × 16-payoff matrix is computed for the limiting case of a vanishingly small noise term affecting the interaction. Some results concerning the evolution of populations of automata under the action of selection are obtained. The special role of win-stay, lose-shift-strategies is examined. 相似文献
6.
Linear birth and death processes are used to derive simple expressions for sequential extinction times and gene fixation probabilities in asexual populations. 相似文献
7.
Rats were food-rationed (15 g/day) and trained to bar-press for food. In Experiment 1, the animals were injected with cholecystokinin octapeptide (CCK, 2 μg/kg), bombesin (BBS, 12 μg/kg), normal saline, or prefed with 20 Noyes 45 mg pellets. The animals were then tested for one hour for bar-pressing responses with food reward. In Experiment 2, the animals were similarly trained, treated, and tested for bar-pressing responses without food reward. The results showed that BBS and prefeeding decreased bar-pressing, rewarded or non-rewarded, but the CCK effect was greatly decreased when food was withheld. It appeared that the CCK effect was more dependent upon the presence of food than the BBS or prefeeding effects. The results were discussed in terms of involvement of the food and reward-related oropharyngeal stimuli for the CCK effect and the drive-related stimuli for the BBS and prefeeding effects. 相似文献
8.
Daniela Beisser Julia Kolter Anna M Sigmund Jörg Steinmann Simon Schäfer Hubertus Hochrein Sven Rahmann Hermann Wagner Philipp Henneke Veit Hornung Jan Buer Carsten J Kirschning 《EMBO reports》2015,16(12):1656-1663
Toll‐like receptor (TLR) 13 and TLR2 are the major sensors of Gram‐positive bacteria in mice. TLR13 recognizes Sa19, a specific 23S ribosomal (r) RNA‐derived fragment and bacterial modification of Sa19 ablates binding to TLR13, and to antibiotics such as erythromycin. Similarly, RNase A‐treated Staphylococcus aureus activate human peripheral blood mononuclear cells (PBMCs) only via TLR2, implying single‐stranded (ss) RNA as major stimulant. Here, we identify human TLR8 as functional TLR13 equivalent that promiscuously senses ssRNA. Accordingly, Sa19 and mitochondrial (mt) 16S rRNA sequence‐derived oligoribonucleotides (ORNs) stimulate PBMCs in a MyD88‐dependent manner. These ORNs, as well as S. aureus‐, Escherichia coli‐, and mt‐RNA, also activate differentiated human monocytoid THP‐1 cells, provided they express TLR8. Moreover, Unc93b1
−/−‐ and Tlr8
−/−‐THP‐1 cells are refractory, while endogenous and ectopically expressed TLR8 confers responsiveness in a UR/URR RNA ligand consensus motif‐dependent manner. If TLR8 function is inhibited by suppression of lysosomal function, antibiotic treatment efficiently blocks bacteria‐driven inflammatory responses in infected human whole blood cultures. Sepsis therapy might thus benefit from interfering with TLR8 function. 相似文献
9.
Spectinomycin resistance due to a mutation in an rRNA operon of Escherichia coli 总被引:3,自引:2,他引:3 下载免费PDF全文
A spectinomycin resistance mutation was isolated in an Escherichia coli rRNA operon (rrnH) located on a multicopy plasmid. Cell-free protein-synthesizing extracts made from cells containing the plasmid were partially resistant to spectinomycin. Although spectinomycin is an aminoglycoside antibiotic, the mutation did not confer resistance to any other aminoglycoside antibiotic tested. 相似文献
10.