全文获取类型
收费全文 | 993篇 |
免费 | 83篇 |
出版年
2023年 | 8篇 |
2021年 | 10篇 |
2020年 | 8篇 |
2019年 | 7篇 |
2018年 | 16篇 |
2017年 | 10篇 |
2016年 | 22篇 |
2015年 | 33篇 |
2014年 | 40篇 |
2013年 | 64篇 |
2012年 | 56篇 |
2011年 | 57篇 |
2010年 | 59篇 |
2009年 | 46篇 |
2008年 | 47篇 |
2007年 | 36篇 |
2006年 | 42篇 |
2005年 | 31篇 |
2004年 | 32篇 |
2003年 | 18篇 |
2002年 | 29篇 |
2001年 | 26篇 |
2000年 | 32篇 |
1999年 | 27篇 |
1998年 | 16篇 |
1997年 | 16篇 |
1996年 | 12篇 |
1995年 | 14篇 |
1994年 | 9篇 |
1993年 | 10篇 |
1992年 | 11篇 |
1991年 | 14篇 |
1990年 | 13篇 |
1989年 | 12篇 |
1988年 | 17篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 9篇 |
1983年 | 8篇 |
1982年 | 21篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 7篇 |
1977年 | 16篇 |
1976年 | 8篇 |
1975年 | 7篇 |
1974年 | 12篇 |
1973年 | 10篇 |
1967年 | 7篇 |
排序方式: 共有1076条查询结果,搜索用时 31 毫秒
61.
62.
Zarnowski R Jaromin A Certik M Czabany T Fontaine J Jakubik T Iqbal MC Grandmougin-Ferjani A Kozubek A Pietr SJ 《Zeitschrift für Naturforschung. C, Journal of biosciences》2004,59(5-6):321-326
The oil of Adenanthera pavonina L. seeds was analysed by chromatographic and instrumental means. The oil was found to be rich in neutral lipids (86.2%), and low in polar lipids (13.8%). The neutral lipids consisted mainly of triacylglycerols (64.2%). Unsaturated fatty acids were found as high as 71%, while the percentage of saturated fatty acids was only 29%. GC and GC/MS analyses revealed linoleic, oleic and lignocerotic acid to be predominant among all fatty acids in the A. pavonina oil, whereas stigmasterol was the major steroid identified within this study. Subsequently, the oil was used for preparation of submicron oil-in-water (o/w) lipid emulsions. Lipid emulsions were formulated by using soybean lecithin (SL) to investigate their particle size, Zeta potential and stability at the different oil and SL ratios. The results obtained indicate possible applications of the tested oil in pharmaceutical and medical fields as drug and cosmetic active ingredient carriers. 相似文献
63.
Géraldine?Verquin Ga?lle?Fontaine Marc?Bria Elena?Zhilinskaya Edmond?Abi-Aad Antoine?Abouka?s Brigitte?Baldeyrou Christian?Bailly Jean-Luc?BernierEmail author 《Journal of biological inorganic chemistry》2004,9(3):345-353
Oxovanadium(IV) complexes of hydroxysalen derivatives have been prepared and tested as DNA reactive agents. The nuclease activity has been investigated under oxidative or reducing conditions, on the basis of the various oxidation states of vanadium: VIII, VIV and VV. In the absence of an activating agent, none of the compounds tested was able to induce cleavage of DNA, whereas in the presence of mercaptopropionic acid (MPA) or Oxone the four complexes induced DNA modifications. Under both conditions, the para-hydroxy complex was found to be the most active compound. Reaction of these salen complexes with DNA occurs essentially at guanine residues and is more efficient in the presence of Oxone than under reducing conditions. The extent of Oxone-mediated DNA oxidation by the four vanadyl complexes was clearly superior to VOSO4
and was observed without piperidine treatment. EPR studies provided information on the reactive metal-oxo species involved under each conditions and a mechanism of reaction with DNA is discussed.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00775-004-0529-0Abbreviations BPE buffer
bis-phosphate EDTA buffer
- DMPO
5,5-dimethylpyrroline
N-oxide
- DMS
dimethyl sulfate
- HFS
hyperfine structure
- Lin
linear
- MPA
3-mercaptopropionic acid
- Nck
nicked
- salen
(salicylidene)ethylenediamine
- Sc
supercoiled
- TBE buffer
tris-borate EDTA buffer
- Tris
tris(hydroxymethyl)aminomethane 相似文献
64.
Johnson KA Angelucci F Bellelli A Hervé M Fontaine J Tsernoglou D Capron A Trottein F Brunori M 《Biochemistry》2003,42(34):10084-10094
Schistomiasis is a debilitating parasitic disease which affects 200 million people, causing life-threatening complications in 10% of the patients. This paper reports the crystal structure of the Schistosoma haematobium 28 kDa glutathione S-transferase, a multifunctional enzyme involved in host-parasite interactions and presently considered as a promising vaccine candidate against schistosomiasis. The structures of the GSH-free enzyme, as well as the partially (approximately 40%) and almost fully (approximately 80%) GSH-saturated enzyme, exhibit a unique feature, absent in previous GST structures, concerning the crucial and invariant Tyr10 side chain which occupies two alternative positions. The canonical conformer, which allows an H-bond to be formed between the side chain hydroxyl group and the activated thiolate of GSH, is somewhat less than 50% occupied. The new conformer, with the phenoxyl ring on the opposite side of the mobile loop connecting strand 1 and helix 1, is stabilized by a polar interaction with the guanidinium group of the conserved Arg21 side chain. The presence of two conformers of Tyr10 may provide a clue about clarifying the multiple catalytic functions of Sh28GST and might prove to be relevant for the design of specific antischistosomal drugs. The K(d) for GSH binding was determined by equilibrium fluorescence titrations to be approximately 3 microM and by stopped-flow rapid mixing experiments to be approximately 9 microM. The relatively tight binding of GSH by Sh28GST explains the residually bound GSH in the crystal and supports a possible role of GSH as a tightly bound cofactor involved in the catalytic mechanism for prostaglandin D(2) synthase activity. 相似文献
65.
Antigen presentation by CD1d contributes to the amplification of Th2 responses to Schistosoma mansoni glycoconjugates in mice 总被引:6,自引:0,他引:6
Faveeuw C Angeli V Fontaine J Maliszewski C Capron A Van Kaer L Moser M Capron M Trottein F 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(2):906-912
During murine schistosomiasis, there is a gradual switch from a predominant Th1 cytokine response to a Th2-dominated response after egg laying, an event that favors the formation of granuloma around viable eggs. Egg-derived glycoconjugates, including glycolipids, may play a crucial role in this phenomenon. In this study, we used a model of dendritic cell sensitization to study the role of egg glycoconjugates in the induction of specific immune response to soluble egg Ag (SEA) and to investigate the possibility that CD1d, a molecule implicated in glycolipid presentation, may be involved in such a phenomenon. We show that, when captured, processed, and presented to naive T lymphocytes by dendritic cells, egg, but not larval, Ag skew the immune response toward a Th2 response. Periodate treatment reversed this effect, indicating that the sugar moiety of SEA is important in this phenomenon. Using DC treated ex vivo with a neutralizing anti-CD1d Ab or isolated from CD1d knockout mice, we show that CD1d is crucial in the priming of SEA-specific Th2 lymphocytes. We then evaluated the contribution of CD1d on the development of the SEA-specific immune response and on the formation of the egg-induced liver granuloma during murine schistosomiasis. We find that CD1d knockout mice have a reduced Th2 response after egg laying and develop a less marked fibrotic pathology compared with wild-type mice. Altogether, our results suggest that Ag presentation of parasite glycoconjugates to CD1d-restricted T cells may be important in the early events leading to the induction of Th2 responses and to egg-induced pathology during murine schistosomiasis. 相似文献
66.
Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60 总被引:20,自引:0,他引:20
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hansen JJ Dürr A Cournu-Rebeix I Georgopoulos C Ang D Nielsen MN Davoine CS Brice A Fontaine B Gregersen N Bross P 《American journal of human genetics》2002,70(5):1328-1332
SPG13, an autosomal dominant form of pure hereditary spastic paraplegia, was recently mapped to chromosome 2q24-34 in a French family. Here we present genetic data indicating that SPG13 is associated with a mutation, in the gene encoding the human mitochondrial chaperonin Hsp60, that results in the V72I substitution. A complementation assay showed that wild-type HSP60 (also known as "HSPD1"), but not HSP60 (V72I), together with the co-chaperonin HSP10 (also known as "HSPE1"), can support growth of Escherichia coli cells in which the homologous chromosomal groESgroEL chaperonin genes have been deleted. Taken together, our data strongly indicate that the V72I variation is the first disease-causing mutation that has been identified in HSP60. 相似文献
67.
In 1984, a species of guenon endemic to Gabon was discovered: the sun-tailed monkey (Cercopithecus solatus). This species is difficult to locate and observe in the wild, and hence to date has been little studied. The Centre International
de Recherches Médicales de Franceville (CIRMF), Gabon, houses the world’s only breeding colony ofC. solatus, on which eco-ethological investigations can be carried out in a semi-free ranging environment. The data reported here present
the first results of observations on the social relationships of this colony and support the scant field observations available
on this species, showing a basic social unit of one adult male and several females with their offspring. The resident male
systematically repulses any second adult male in proximity to the group. A clear hierarchy exists among the females, with
mature female offspring eventually acquiring a rank just below that of their mother. 相似文献
68.
Bocquet-Muchembled B Leroux R Chotteau-Lelièvre A Vergoten G Fontaine F 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,132(4):685-697
The Ets family includes numerous proteins with a highly conserved DNA-binding domain of 85 amino acids named the ETS domain. Phylogenetic analyses from ETS domains revealed that this family could be divided into 13 groups, among them are ETS and ERG. The ets genes are present in the Metazoan kingdom and we have previously characterized the Nd ets and Nd erg genes in the polychaete annelid Hediste diversicolor. Here, we isolated a fragment encoding the ETS domain from Nd Ets, by genomic library screening. By Northern blot analysis, we showed that this gene was transcribed as one major mRNA of 2.6 kb and one minor mRNA of 3.2 kb. By in situ hybridization, we observed that Nd ets was expressed in the intestine and oocytes and that Nd erg was expressed in cellular clumps present in the coelomic cavity, in an area of proliferating cells situated between the last metamere and the pygidium. Finally, we showed that Nd erg shared the expression pattern of Nd ets in oocytes. Molecular modeling studies have revealed that the spatial structure of ETS domain of Nd Ets and Nd Erg was conserved, in comparison to the murine Ets-1 and human Fli-1 proteins, respectively. 相似文献
69.
Nogueira V Walter L Avéret N Fontaine E Rigoulet M Leverve XM 《Journal of bioenergetics and biomembranes》2002,34(1):55-66
Thyroid status is crucial in energy homeostasis, but despite extensive studies the actual mechanism by which it regulates mitochondrial respiration and ATP synthesis is still unclear. We studied oxidative phosphorylation in both intact liver cells and isolated mitochondria from in vivo models of severe not life threatening hyper- and hypothyroidism. Thyroid status correlated with cellular and mitochondrial oxygen consumption rates as well as with maximal mitochondrial ATP production. Addition of a protonophoric uncoupler, 2,4-dinitrophenol, to hepatocytes did not mimic the cellular energetic change linked to hyperthyroidism. Mitochondrial content of cytochrome oxidase, ATP synthase, phosphate and adenine nucleotide carriers were increased in hyperthyroidism and decreased in hypothyroidism as compared to controls. As a result of these complex changes, the maximal rate of ATP synthesis increased in hyperthyroidism despite a decrease in ATP/O ratio, while in hypothyroidism ATP/O ratio increased but did not compensate for the flux limitation of oxidative phosphorylation. We conclude that energy homeostasis depends on a compromise between rate and efficiency, which is mainly regulated by thyroid hormones. 相似文献
70.
Nielsen SL Nygaard H Mandrup L Fontaine AA Hasenkam JM He S Yoganathan AP 《Journal of biomechanical engineering》2002,124(5):596-608
Clinically observed incomplete mitral leaflet coaptation was reproduced in vitro by altering the balance of the chordal tethering and chordal coapting force components. Mitral leaflet coaptation geometry was distorted by changes of the spatial relations between the papillary muscles and the mitral valve as well as hemodynamics. Mitral leaflet malalignment was accentuated by a redistribution of the chordal tethering and coapting force components. For the overall assessment of systolic mitral leaflet configuration in functional mitral regurgitation it is important to consider the interaction between chordal restraint and an altered mitral leaflet coaptation geometry. 相似文献