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21.
ARTC1-mediated ADP-ribosylation of GRP78/BiP: a new player in endoplasmic-reticulum stress responses
22.
Houlden H Johnson J Gardner-Thorpe C Lashley T Hernandez D Worth P Singleton AB Hilton DA Holton J Revesz T Davis MB Giunti P Giunti P Wood NW 《Nature genetics》2007,39(12):1434-1436
The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration. 相似文献
23.
Paola Luciani Cristiana Deledda Susanna Benvenuti Ilaria Cellai Roberta Squecco Monica Monici Francesca Cialdai Giorgia Luciani Giovanna Danza Chiara Di Stefano Fabio Francini Alessandro Peri 《Cellular and molecular life sciences : CMLS》2010,67(21):3711-3723
Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide with neurotrophic properties, as assessed in animal cell models. Exendin-4, a GLP-1 analogue, has been recently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to morphologically, structurally, and functionally characterize the differentiating actions of exendin-4 using a human neuronal cell model (i.e., SH-SY5Y cells). We found that exendin-4 increased the number of neurites paralleled by dramatic changes in intracellular actin and tubulin distribution. Electrophysiological analyses showed an increase in cell membrane surface and in stretch-activated-channels sensitivity, an increased conductance of Na+ channels and amplitude of Ca++ currents (T- and L-type), typical of a more mature neuronal phenotype. To our knowledge, this is the first demonstration that exendin-4 promotes neuronal differentiation in human cells. Noteworthy, our data support the claimed favorable role of exendin-4 against diabetic neuropathy as well as against different neurodegenerative diseases. 相似文献
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Monica Bari Tiziana Bonifacino Marco Milanese Paola Spagnuolo Simona Zappettini Natalia Battista Francesco Giribaldi Cesare Usai Giambattista Bonanno Mauro Maccarrone 《Cellular and molecular life sciences : CMLS》2011,68(5):833-845
The endocannabinoid system and endocannabinoid receptor-driven modulation of glutamate release were studied in rat brain cortex
astroglial gliosomes. These preparations contained the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, as well their major biosynthetic (N-acyl-phosphatidylethanolamines-hydrolyzing-phospholipase D and diacylglycerol-lipase) and catabolic (fatty acid amide-hydrolase
and monoacylglycerol-lipase) enzymes. Gliosomes expressed type-1 (CB1R), type-2 (CB2R) cannabinoid, and type-1 vanilloid (TRPV1)
receptors, as ascertained by Western blotting and confocal microscopy. Methanandamide, a stable analogue of anandamide acting
as CB1R, CB2R, and TRPV1 agonist, stimulated or inhibited the depolarization-evoked gliosomal [3H]d-aspartate release, at lower and higher concentrations, respectively. Experiments with ACEA (arachidonyl-2′-chloroethylamide),
JWH133 ((6aR,10aR)-3-(1,1-dimethylbutyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]-pyran) and capsaicin, selective
agonists at CB1R, CB2R and TRPV1, respectively, demonstrated that potentiation of [3H]d-aspartate release was due to CB1R while inhibition to CB2R and TRPV1 engagement. These findings were confirmed by using selective
receptor antagonists. Furthermore, CB1R activation caused increase of intracellular IP3 and Ca2+ concentration, suggesting an involvement of phospholipase C. 相似文献
26.
Proteome survey reveals modularity of the yeast cell machinery 总被引:4,自引:0,他引:4
Gavin AC Aloy P Grandi P Krause R Boesche M Marzioch M Rau C Jensen LJ Bastuck S Dümpelfeld B Edelmann A Heurtier MA Hoffman V Hoefert C Klein K Hudak M Michon AM Schelder M Schirle M Remor M Rudi T Hooper S Bauer A Bouwmeester T Casari G Drewes G Neubauer G Rick JM Kuster B Bork P Russell RB Superti-Furga G 《Nature》2006,440(7084):631-636
Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. Through systematic tagging of open reading frames (ORFs), the majority of complexes were purified several times, suggesting screen saturation. The richness of the data set enabled a de novo characterization of the composition and organization of the cellular machinery. The ensemble of cellular proteins partitions into 491 complexes, of which 257 are novel, that differentially combine with additional attachment proteins or protein modules to enable a diversification of potential functions. Support for this modular organization of the proteome comes from integration with available data on expression, localization, function, evolutionary conservation, protein structure and binary interactions. This study provides the largest collection of physically determined eukaryotic cellular machines so far and a platform for biological data integration and modelling. 相似文献
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Segregation of receptor and ligand regulates activation of epithelial growth factor receptor 总被引:17,自引:0,他引:17
Vermeer PD Einwalter LA Moninger TO Rokhlina T Kern JA Zabner J Welsh MJ 《Nature》2003,422(6929):322-326
Interactions between ligands and receptors are central to communication between cells and tissues. Human airway epithelia constitutively produce both a ligand, the growth factor heregulin, and its receptors--erbB2, erbB3 and erbB4 (refs 1-3). Although heregulin binding initiates cellular proliferation and differentiation, airway epithelia have a low rate of cell division. This raises the question of how ligand-receptor interactions are controlled in epithelia. Here we show that in differentiated human airway epithelia, heregulin-alpha is present exclusively in the apical membrane and the overlying airway surface liquid, physically separated from erbB2-4, which segregate to the basolateral membrane. This physical arrangement creates a ligand-receptor pair poised for activation whenever epithelial integrity is disrupted. Indeed, immediately following a mechanical injury, heregulin-alpha activates erbB2 in cells at the edge of the wound, and this process hastens restoration of epithelial integrity. Likewise, when epithelial cells are not separated into apical and basolateral membranes ('polarized'), or when tight junctions between adjacent cells are opened, heregulin-alpha activates its receptor. This mechanism of ligand-receptor segregation on either side of epithelial tight junctions may be vital for rapid restoration of integrity following injury, and hence critical for survival. This model also suggests a mechanism for abnormal receptor activation in diseases with increased epithelial permeability. 相似文献
29.
Loftus B Anderson I Davies R Alsmark UC Samuelson J Amedeo P Roncaglia P Berriman M Hirt RP Mann BJ Nozaki T Suh B Pop M Duchene M Ackers J Tannich E Leippe M Hofer M Bruchhaus I Willhoeft U Bhattacharya A Chillingworth T Churcher C Hance Z Harris B Harris D Jagels K Moule S Mungall K Ormond D Squares R Whitehead S Quail MA Rabbinowitsch E Norbertczak H Price C Wang Z Guillén N Gilchrist C Stroup SE Bhattacharya S Lohia A Foster PG Sicheritz-Ponten T Weber C Singh U Mukherjee C El-Sayed NM 《Nature》2005,433(7028):865-868
Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen. 相似文献
30.
R. Tritapepe C. Di Padova Paola Rovagnati 《Cellular and molecular life sciences : CMLS》1980,36(5):580-581
Summary The spontaneous reversal of ethinyl estradiol-induced cholestasis has been documented 7 days after the last estrogen administration in the rat. This finding supports the hypothesis that estrogens produce only a transient functional failure of the hepatocytic structures responsible for bile secretion.Supported by Research grant CT-77, 0153304 from Consiglio Nazionale delle Ricerche, Rome, Italy. 相似文献