首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   453篇
  免费   46篇
  2023年   2篇
  2022年   2篇
  2021年   8篇
  2020年   2篇
  2019年   8篇
  2018年   14篇
  2017年   13篇
  2016年   12篇
  2015年   18篇
  2014年   18篇
  2013年   29篇
  2012年   26篇
  2011年   19篇
  2010年   13篇
  2009年   14篇
  2008年   21篇
  2007年   14篇
  2006年   20篇
  2005年   25篇
  2004年   29篇
  2003年   26篇
  2002年   12篇
  2001年   18篇
  2000年   18篇
  1999年   12篇
  1998年   9篇
  1997年   3篇
  1996年   3篇
  1995年   4篇
  1994年   7篇
  1993年   5篇
  1992年   6篇
  1991年   10篇
  1990年   6篇
  1989年   9篇
  1988年   8篇
  1987年   6篇
  1986年   3篇
  1985年   8篇
  1984年   5篇
  1983年   3篇
  1982年   1篇
  1981年   2篇
  1976年   1篇
  1975年   2篇
  1974年   1篇
  1973年   1篇
  1968年   1篇
  1966年   1篇
  1964年   1篇
排序方式: 共有499条查询结果,搜索用时 15 毫秒
61.
Omnes  M. H.  Recek  S.  Barone  H.  Le Delliou  H.  Schmitz  A.  Mutelet  A.  Suquet  M.  & Robin  J. H. 《Journal of fish biology》2004,65(S1):333-333
Four‐year‐old pollack Pollachius pollachius L., previously fed on dry pellets since their juvenile stage, were divided into three experimental groups two months prior their first spawning season. They were fed a commercial broodstock pellet enriched with 6% added oils, either: (1) capelin oil (control), (2) capelin oil plus arachidonic acid, or (3) DHA rich tuna oil. Spawning performance was determined in each group and egg lipids were analysed. During the vitellogenic period, the estradiol levels in plasma increased with oocyte enlargement, indicating that captivity and pelleted feed did not affect reproductive capacity. Females from each group spawned spontaneously between February and May. Egg production per kg of female was highest in the control group. Fertilization rate was highest (39%) in the group fed on diet enhanced in DHA. Lipid content in eggs reached 16% of dry mass, containing mainly phospholipids (75%). Egg fatty acid profiles showed few differences between dietary treatments. There was no significant difference in the concentration of Docosahexaenoic acid (22:6n − 3) between groups. Arachidonic acid (20:4n − 6) was lower in neutral and polar lipids of eggs from the control group than in the other groups. Tuna oil diet induced the highest DHA/EPA ratio in eggs and seemed to provide sufficient arachidonic acid for pollack broodstock. Egg fatty acid profiles are compared with 6 year‐old pollack broodstock fed on fish, and with other cultured and wild fish species.  相似文献   
62.
The 23Na NMR quadrupolar relaxation in NaDNA aqueous solutions has been investigated in the presence of (+) and (−) arabitol. Quite different results were produced by the enantiomers, i.e. the addition of (+) arabitol produced a small increase of the 23Na NMR relaxation rates, while in the presence of (−) arabitol a significant decrease was observed. These findings were analysed and discussed in terms of an effective interaction of (−) arabitol with DNA.  相似文献   
63.
64.
65.
66.
The use of microalgae in a number of sectors, including biodiesel, feed and food production, is proving to be of great interest. An evaluation was made of the possible biostimulant effects on Chlorella vulgaris and Scenedesmus quadricauda of humic-like substances (HLs) extracted from agro-industrial wastes. These included digestate from the waste of an agro-livestock farm (D-HL), oil extraction residues from rape (B-HL, Brassica napus L.) and tomato residues (T-HL). The microalgal growth medium (BG11) was supplemented with HLs to evaluate their effect on biomass yield as well as carbohydrate, chlorophylls a and b, lipid and fatty acid contents. Our results showed that the HLs used in the test are effective biostimulants of C. vulgaris and S. quadricauda. The biostimulant effect seems to depend on the type of extract used for cultivating the microalgae, the concentration and the species treated. Among the extracts applied to the growth medium, D-HL and T-HL seem to have a significant effect on microalgal biomass and lipid production. Although B-HL showed no significant effect on the biomass and lipid content of C. vulgaris and S. quadricauda, its presence in the growth medium increased the saturated:unsaturated fatty acid ratio (SFA/UFA) and stimulated the sugar metabolism of the microalgae by increasing their carbohydrate and chlorophyll content.  相似文献   
67.

Background

Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in > 80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence.

Methods

UV–Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics.

Results

TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na+ or K+. T-Jump kinetic experiments show that the rates of formation and dissociation of these complexes in the ms time scale differ by one order of magnitude. MD simulations reveal that, in K+ buffer, “hybrid 1” conformation yields kinetic constants on interaction with TMPyP4 one order lower than “hybrid 2”. The binding involves π–π stacking with external loop bases.

Conclusions

For the first time we show that for a particular buffer TMPyP4 interacts in a kinetically different way with the two Tel22 conformations even if the complexes formed are thermodynamically indistinguishable.

General significance

G-quadruplexes, endowed with technological applications and potential impact on regulation mechanisms, define a new research field. The possibility of building different conformations from same sequence is a complex issue that confers G-quadruplexes very interesting features. The obtaining of reliable kinetic data constitutes an efficient tool to determine reaction mechanisms between conformations and small molecules.  相似文献   
68.
DNA adducts associated with oxidative stress are believed to involve the formation of endogenous reactive species generated by oxidative damage and lipid peroxidation. Although these adducts have been reported in several human tissues by different laboratories, a comparison of the levels of these adducts in the same tissue samples has not been carried out. In this study, we isolated DNA from the pancreas of 15 smokers and 15 non-smokers, and measured the levels of 1,N6-etheno(2′-deoxy)guanosine (edA), 3,N4-etheno(2′-deoxy)cytidine (edC), 8-oxo-2′-deoxyguanosine (8-oxo-dG), and pyrimido[1,2-]purin-10(3H)-one (m1G). Using the same DNA, the glutathione S-transferase (GST) M1, GSTT1, and NAD(P)H quinone reductase-1 (NQO1) genotypes were determined in order to assess the role of their gene products in modulating adduct levels through their involvement in detoxification of lipid peroxidation products and redox cycling, respectively. The highest adduct levels observed were for m1G, followed by 8-oxo-dG, edA, and edC, but there were no differences in adduct levels between smokers and non-smokers and no correlation with the age, sex or body mass index of the subject. Moreover, there was no correlation in adduct levels between edA and eC, or between edA or edC and m1G or 8-oxo-dG. However, there was a significant correlation (r=0.76; p<0.01) between the levels of 8-oxo-dG and m1G in human pancreas DNA. Neither GSTM1 nor NQO1 genotypes were associated with differences in any of the adduct levels. Although the sample set was limited, the data suggest that endogenous DNA adduct formation in human pancreas is not clearly derived from cigarette smoking or from (NQO1)-mediated redox cycling. Further, it appears that neither GSTM1 nor GSTT1 appreciably protects against endogenous adduct formation. Together with the lack of correlation between m1G and edA or edC, these data indicate that the malondialdehyde derived from lipid peroxidation may not contribute significantly to m1G adduct formation. On the other hand, the apparent correlation between m1G and 8-oxo-dG and their comparable high levels are consistent with the hypothesis that m1G is formed primarily by reaction of DNA with a base propenal, which, like 8-oxo-dG, is thought to be derived from hydroxyl radical attack on the DNA.  相似文献   
69.
70.
Large bowel carcinogenesis involves accumulation of genetic alterations leading to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It is pertinent to elucidate the molecular changes occurring in the pre-neoplastic lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps), many of which are molecular chaperones, are implicated in carcinogenesis, and their variations with tumor progression encourage their study as biomarkers. There are many reports on Hsps and cancer but none to our knowledge on their systematic quantification in pre-neoplastic lesions of the large bowel. We performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, and Hsp90 in biopsies of large bowel tubular adenomas with moderate grade of dysplasia and compared to normal mucosa and adenocarcinoma with a moderate grade of differentiation (G2). A significant elevation of Hsp10 and Hsp60 only, i.e., in the absence of elevation of Hsp70 or Hsp90, in both epithelium and lamina propria was found in tubular adenoma by comparison with normal mucosa. In contrast, adenocarcinoma was characterized by the highest levels of Hsp10 and Hsp60 in epithelium and lamina propria, accompanied by the highest levels of Hsp70 only in epithelium and of Hsp90 only in lamina propria, by comparison with normal and tubular adenoma counterparts. Hsp10 and Hsp60 are promising biomarkers for early diagnosis of tubular adenoma and for its differentiation from more advanced malignant lesions. Hsp10 and Hsp60 may be implicated in carcinogenesis from its very early steps and, thus, are potentially convenient targets for therapy.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号