全文获取类型
收费全文 | 725篇 |
免费 | 71篇 |
出版年
2023年 | 3篇 |
2022年 | 11篇 |
2021年 | 16篇 |
2020年 | 12篇 |
2019年 | 16篇 |
2018年 | 22篇 |
2017年 | 14篇 |
2016年 | 18篇 |
2015年 | 43篇 |
2014年 | 35篇 |
2013年 | 59篇 |
2012年 | 60篇 |
2011年 | 54篇 |
2010年 | 36篇 |
2009年 | 32篇 |
2008年 | 30篇 |
2007年 | 40篇 |
2006年 | 35篇 |
2005年 | 33篇 |
2004年 | 27篇 |
2003年 | 30篇 |
2002年 | 25篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 10篇 |
1994年 | 9篇 |
1993年 | 6篇 |
1992年 | 12篇 |
1991年 | 11篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1980年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1971年 | 2篇 |
1967年 | 2篇 |
1964年 | 2篇 |
排序方式: 共有796条查询结果,搜索用时 15 毫秒
91.
Mandili G Khadjavi A Gallo V Minero VG Bessone L Carta F Giribaldi G Turrini F 《The FEBS journal》2012,279(12):2182-2191
Doxorubicin is commonly considered to exert its anti-tumor activity by triggering apoptosis of cancer cells through DNA damage. Recent reports have shown that Doxorubicin elicits a marked heat shock response, and that either inhibition or silencing of heat shock proteins enhance the Doxorubicin apoptotic effect in neuroblastoma cells. In order to investigate whether Doxorubicin may also act through protein modification, we performed a proteomic analysis of ubiquitinated proteins. Here we show that nanomolar Doxorubicin treatment of neuroblastoma cells caused: (a) dose-dependent over-ubiquitination of a specific set of proteins in the absence of measurable inhibition of proteasome, (b) protein ubiquination patterns similar to those with Bortezomib, a proteasome inhibitor, (c) depletion and loss of activity of ubiquitinated enzymes such as lactate dehydrogenase and α-enolase, and (d) a decrease in HSP27 solubility, probably a consequence of its binding to denatured proteins. These data strongly reinforce the hypothesis that Doxorubicin may also exert its effect by damaging proteins. 相似文献
92.
Bramanti V Bronzi D Tomassoni D Costa A Raciti G Avitabile M Amenta F Avola R 《Neurochemical research》2008,33(12):2593-2600
In this research we aimed to investigate the interactions between growth factors (GFs) and dexamethasone (DEX) on cytoskeletal
proteins GFAP and vimentin (VIM) expression under different experimental conditions. Condition I: 24 h pretreatment with bFGF,
subsequent 72 h switching in serum-free medium (SFM) and final addition of GFs, alone or by two in the last 24 h, after a
prolonged (60 h) DEX treatment. Condition II: 36 h pretreatment with DEX (with bFGF in the last 24 h), followed by SFM for
60 h and final addition for 24 h with growth factors alone or two of them togheter. Western blot analysis data showed a marked
GFAP expression in cultures submitted to Condition I comparing results to untreated or treated controls. VIM expression was
instead significantly reduced after GFs addition in the last 24 h of 60 h DEX treatment, respect to control DEX-pretreated
ones. Referring data to untreated controls, VIM expression was significantly enhanced after GFs addition. GFAP showed also
a significant increase in astrocytes submitted to Condition II, respect to untreated or treated control cultures. VIM expression
was up and down regulated under Condition II. Collectively, our findings evidence an interactive dialogue between GFs and
DEX in astroglial cultures, co-pretreated with DEX and bFGF, regulating cytoskeletal network under stressfull conditions.
Special issue article in honor of Dr. Anna Maria Giuffrida-Stella. 相似文献
93.
Perrino E Cappelletti G Tazzari V Giavini E Del Soldato P Sparatore A 《Bioorganic & medicinal chemistry letters》2008,18(6):1893-1897
One dithiolthione and two new methanethiosulfonate derivatives of valproic acid (VPA) were synthesized and tested in vitro as histone deacetylase (HDAC) inhibitors. The new molecules, as well as their sulfurated moieties, exhibited a much stronger inhibition of HDAC enzymatic and antiproliferative activities and histone hyperacetylation than VPA. ACS 2 is the most interesting compound among the new VPA derivatives and its sulfurated moiety, 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione, also known to be a metabolite of anethole trithione, seems to contribute significantly to its activity. This is the first time that HDAC inhibitory activity is described for dithiolethiones and thiosulfonates. 相似文献
94.
The interactions between zinc(II) and the two ligands 2-hydroxynicotinic acid (HNic) and 3-hydroxypicolinic acid (HPic) have been investigated by means of potentiometric titrations in aqueous 0.6 m (Na)Cl at 25 °C. In both cases, only mononuclear complexes are formed. The qualitative and quantitative results obtained have been confirmed in part by UV-Vis spectrophotometry and 1H NMR spectroscopy. The complex trans-diaqua-bis-(3-hydroxypicolinato)zinc(II) was obtained as a crystal and examined by X-ray crystallography. The thermodynamic results allow drawing some conclusions regarding the extent of Zn(II) interference in a hypothetical chelation therapy treatment of aluminium or iron overload with these two ligands. 相似文献
95.
Guiseppina Mignogna Roberta Chiaraluce Valerio Consalvi Stefano Cavallo Simonetta Stefanini Emilia Chiancone 《European journal of biochemistry》2002,269(6):1600-1606
Ferritin from the spleen of the Antarctic teleost Trematomus bernacchii is composed of a single subunit that contains both the ferroxidase center residues, typical of mammalian H chains, and the carboxylate residues forming the micelle nucleation site, typical of mammalian L chains. Comparison of the amino-acid sequence with those available from lower vertebrates indicates that T. bernacchii ferritin can be classified as an M-type homopolymer. Interestingly, the T. bernacchii ferritin chain shows 85.7% identity with a cold-inducible ferritin chain of the rainbow trout Salmo gairdneri. The structural and functional properties indicate that cold acclimation and functional adaptation to low temperatures are achieved without significant modification of the protein stability. In fact, the stability of T. bernacchii ferritin to denaturation induced by acid or temperature closely resembles that of mesophilic mammalian ferritins. Moreover iron is taken up efficiently and the activation energy of the reaction is 74.9 kJ.mol(-1), a value slightly lower than that measured for the human recombinant H ferritin (80.8 kJ.mol(-1)). 相似文献
96.
Valerio Zupo 《Hydrobiologia》2001,449(1-3):131-140
The gut contents of the shrimp Hippolyte inermis were investigated for 1 year along a depth transect through a seagrass bed. Besides size, sex and weight of all individuals were recorded. The diets of immature and adult individuals were compared to detect any influence of food on sex development, since previous investigations indicated a correlation of the life cycle of this protandric species with the abundance of algal food in the environment, and laboratory experiments demonstrated the effect of diatoms of the genus Cocconeis on the direct development of females. Results indicated that the shrimp is an opportunistic herbivore, able to feed on both plant and animal items, with a preference for macroalgae and diatoms present on the leaves of Posidonia oceanica. Small females, deriving from direct differentiation, had a diet significantly different from that of males. The difference was due to a larger abundance of microalgae in the guts of young females. The influence of microalgal food on the sex reversal mechanism of this species, previously detected through laboratory experiments, was demonstrated to control the life cycle of H. inermis in the field. 相似文献
97.
A new minimal synthetic medium, with low amount of glucose, without aminoacids, vitamins and neutral pH, which induces germ-tubes production in Candida albicans, is reported in this work. The results indicate a perfect agreement between the germ-tube test performed with the standard method in human or animal serum and this test performed in minimal synthetic medium. In this medium the germ-tube test for the presumptive identification of Candida albicans can be performed with the same formality, time and reproducibility as those in human or animal serum. This constitutes an interesting finding because it is easy to prepare, to store and is highly reproducible. 相似文献
98.
99.
100.
Valerio Chiroli Minerva R. Batugo Stefano Biondi Annalisa Bonfanti Stefania Brambilla David C. Gale Lin Li Daniela Miglietta Fabio Nicoli Ganesh A. Prasanna Daniela Ronchetti William F. Vernier Wesley K.M. Chong 《Bioorganic & medicinal chemistry letters》2009,19(10):2785-2788
A novel class of timolol derivatives with nitric oxide (NO)-donating moieties achieved chemical stability yet under physiologically relevant conditions released timolol and NO. Hindered esters A were designed and synthesized, whose ‘triggered’ release relied on enzymatic hydrolysis of the nitrate ester in A to B, that in turn cyclized to liberate timolol. 相似文献