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51.
Johnson-Cadwell LI Jekabsons MB Wang A Polster BM Nicholls DG 《Journal of neurochemistry》2007,101(6):1619-1631
Cultured rat cerebellar granule neurons were incubated with low nanomolar concentrations of the protonophore carbonylcyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) to test the hypothesis that 'mild uncoupling' could be neuroprotective by decreasing oxidative stress. To quantify the uncoupling, respiration and mitochondrial membrane potential (Deltapsi(m)) were determined in parallel as a function of FCCP concentration. Deltapsi(m) dropped by less than 10 mV before respiratory control was lost. Conditions for the valid estimation of matrix superoxide levels were determined from the rate of oxidation of the matrix-targeted fluorescent probe MitoSOX. No significant change in the level of matrix superoxide could be detected on addition of FCCP while respiratory control was retained, although cytoplasmic superoxide levels measured by dihydroethidium oxidation increased. 'Mild uncoupling' by 30 nmol/L FCCP did not alleviate neuronal dysregulation induced by glutathione depletion and significantly enhanced that due to menadione-induced oxidative stress. Low protonophore concentrations enhanced N-methyl-d-aspartate receptor-induced delayed calcium deregulation consistent with a decrease in the spare respiratory capacity available to match the bioenergetic demand of chronic receptor activation. It is concluded that the 'mild uncoupling' hypothesis is not supported by this model. 相似文献
52.
Zhang Z Wakabayashi N Wakabayashi J Tamura Y Song WJ Sereda S Clerc P Polster BM Aja SM Pletnikov MV Kensler TW Shirihai OS Iijima M Hussain MA Sesaki H 《Molecular biology of the cell》2011,22(13):2235-2245
Previous studies using in vitro cell culture systems have shown the role of the dynamin-related GTPase Opa1 in apoptosis prevention and mitochondrial DNA (mtDNA) maintenance. However, it remains to be tested whether these functions of Opa1 are physiologically important in vivo in mammals. Here, using the Cre-loxP system, we deleted mouse Opa1 in pancreatic beta cells, in which glucose-stimulated ATP production in mitochondria plays a key role in insulin secretion. Beta cells lacking Opa1 maintained normal copy numbers of mtDNA; however, the amount and activity of electron transport chain complex IV were significantly decreased, leading to impaired glucose-stimulated ATP production and insulin secretion. In addition, in Opa1-null beta cells, cell proliferation was impaired, whereas apoptosis was not promoted. Consequently, mice lacking Opa1 in beta cells develop hyperglycemia. The data suggest that the function of Opa1 in the maintenance of the electron transport chain is physiologically relevant in beta cells. 相似文献
53.
The R-spondin protein family 总被引:1,自引:0,他引:1
The four vertebrate R-spondin proteins are secreted agonists of the canonical Wnt/β-catenin signaling pathway. These proteins are approximately 35 kDa, and are characterized by two amino-terminal furin-like repeats, which are necessary and sufficient for Wnt signal potentiation, and a thrombospondin domain situated more towards the carboxyl terminus that can bind matrix glycosaminoglycans and/or proteoglycans. Although R-spondins are unable to initiate Wnt signaling, they can potently enhance responses to low-dose Wnt proteins. In humans, rare disruptions of the gene encoding R-spondin1 cause a syndrome of XX sex reversal (phenotypic male), palmoplantar keratosis (a thickening of the palms and soles caused by excess keratin formation) and predisposition to squamous cell carcinoma of the skin. Mutations in the gene encoding R-spondin4 cause anonychia (absence or hypoplasia of nails on fingers and toes). Recently, leucine-rich repeat-containing G-protein-coupled receptor (Lgr)4, Lgr5 and Lgr6, three closely related orphans of the leucine-rich repeat family of G-protein-coupled receptors, have been identified as receptors for R-spondins. Lgr5 and Lgr6 are markers for adult stem cells. Because R-spondins are potent stimulators of adult stem cell proliferation in vivo and in vitro, these findings might guide the therapeutic use of R-spondins in regenerative medicine. 相似文献
54.
Polster BM Robertson CL Bucci CJ Suzuki M Fiskum G 《Cell death and differentiation》2003,10(3):365-370
Bax mediates cytochrome c release and apoptosis during neurodevelopment. Brain mitochondria that were isolated from 8-day, 17-day, and adult rats displayed decreasing levels of mitochondrial Bax. The amount of cytochrome c released from brain mitochondria by a peptide containing the BH3 cell death domain decreased with increasing age. However, approximately 60% of cytochrome c in adult brain mitochondria could be released by the BH3 peptide in the presence of exogenous human recombinant Bax. Mitochondrial Bax was downregulated in PC12S neural cells differentiated with nerve growth factor, and mitochondria isolated from these cells demonstrated decreased sensitivity to BH3-peptide-induced cytochrome c release. These results demonstrate that immature brain mitochondria and mitochondria from undifferentiated neural cells are particularly sensitive to cytochrome c release mediated by endogenous Bax and a BH3 death domain peptide. Postnatal developmental changes in mitochondrial Bax levels may contribute to the increased susceptibility of neurons to pathological apoptosis in immature animals. 相似文献
55.
Mucosal immunization with live recombinant bovine respiratory syncytial virus (BRSV) and recombinant BRSV lacking the envelope glycoprotein G protects against challenge with wild-type BRSV 下载免费PDF全文
Recombinant bovine respiratory syncytial virus (rBRSV) and an rBRSV deletion mutant lacking the G gene (rBRSVDeltaG) were characterized in calves with respect to replication competence, attenuation, and protective efficacy as live-attenuated BRSV vaccines. Both recombinant viruses were safe and induced protection against a BRSV challenge infection. rBRSV replicated efficiently in the upper respiratory tract. Intranasal immunization with rBRSVDeltaG led to infection but not to mucosal virus replication. Neutralizing antibodies were induced by rBRSV and rBRSVDeltaG. Thus, the BRSV attachment glycoprotein G seems to be dispensable in vaccinating calves against BRSV. 相似文献
56.
Cellular Bcl-2 family proteins regulate a critical step in the mammalian programmed cell death pathway by modulating mitochondrial permeability and function. Bcl-2 family proteins are also encoded by several large DNA viruses, including all known gamma herpesviruses, adenoviruses, and several other unrelated viruses. Viral Bcl-2 proteins can prevent cell death but often escape cellular regulatory mechanisms that govern their cellular counterparts. By evading the "altruistic" suicide of infected cells, viruses can ensure replication and propagation in the infected host, but sometimes in surprising ways. Many human cancers and other disorders are associated with viruses that encode Bcl-2 homologs. Here we consider the available mechanistic data for viral compared to cellular Bcl-2 protein function along with relevance to the virus life cycle and human disease states. 相似文献
57.
Neumann LM Polster T Spantzel T Bartsch O 《Genetic counseling (Geneva, Switzerland)》2004,15(1):19-26
Monosomy 1p36 may result in a clinically recognizable chromosomal microdeletion syndrome. We report the unexpected death of a 12 year old boy with mildly dysmorphic facial features, short stature at 138 cm (3rd centile), moderate mental retardation and a history of seizures, obesity, transient muscle weakness of the right arm and leg and episodes of transient atonic hemiparesis of the right side of the body. Despite the relatively few congenital anomalies and normal karyotype, the 1p36 deletion was suspected on clinical grounds and was demonstrated by fluorescent in situ hybridisation (FISH). Two months after diagnosis and following a short history of a mild upper airway infection, high fever and severe diarrhea, the patient had a massive circulatory shock and asystolia, resulting in deep coma, brain edema, apallic syndrome and death. To our knowledge there has been no previous report of episodes of transient unilateral muscle weakness and atonic hemiparesis, circulatory shock and sudden death associated with monosomy 1p36. 相似文献
58.
A 522-base-long Y-chromosomal sequence was isolated from a BALB/c genomic
library and was designated "BF046." It is repeated about 200 times in the
male genome, and a difference was detected between the Mus musculus
musculus and the M. m. domesticus type Y chromosomes. BF046- related
sequences were present over the entire length of the Y chromosome as
visualized by in situ hybridization. Southern blot analysis against DNAs
isolated from eight species in the genus Mus showed that BF046-related
sequences were amplified in the Y chromosomes of three closely related
species: M. musculus, M. spicilegus, and M. spretus. To gain insight into
the stability of the BF046 sequence family, we isolated 18 additional
clones from these three mouse species and compared their sequences. The M.
musculus sequences differed from the M. spicilegus and M. spretus sequences
by two indels. The remaining parts of the sequences were very similar, but
both parsimony and distance-based analytical methods divided the sequences
into the same four subgroups, with each species having its own subgroup(s).
Thus, the Y chromosomes of M. musculus, M. spicilegus, and M. spretus can
be distinguished from one another.
相似文献
59.
Angstrom J; Teneberg S; Milh MA; Larsson T; Leonardsson I; Olsson BM; Halvarsson MO; Danielsson D; N aslund I; Ljungh A; Wadstrom T; Karlsson KA 《Glycobiology》1998,8(4):297-309
The possible role of glycosphingolipids as adhesion receptors for the human
gastric pathogen Helicobacter pylori was examined by use of radiolabeled
bacteria, or protein extracts from the bacterial cell surface, in the
thin-layer chromatogram binding assay. Of several binding specificities
found, the binding to lactosylceramide is described in detail here, the
others being reported elsewhere. By autoradiography a preferential binding
to lactosylceramide having sphingosine/phytosphingosine and 2-D hydroxy
fatty acids was detected, whereas lactosylceramide having sphingosine and
nonhydroxy fatty acids was consistently nonbinding. A selective binding of
H. pylori to lactosylceramide with phytosphingosine and 2-D hydroxy fatty
acid was obtained when the different lactosylceramide species were
incorporated into liposomes, but only in the presence of cholesterol,
suggesting that this selectivity may be present also in vivo . Importantly,
lactosylceramide with sphingosine and hydroxy fatty acids does not bind in
this assay. Furthermore, a lactosylceramide-based binding pattern obtained
for different trisaccharide glycosphingolipids is consistent with the
assumption that this selectivity is due to binding of a conformation of
lactosylceramide in which the oxygen of the 2-D fatty acid hydroxyl group
forms a hydrogen bond with the Glc hydroxy methyl group, yielding an
epitope presentation different from other possible conformers. An
alternative conformation that may come into consideration corresponds to
the crystal structure found for cerebroside, in which the fatty acid
hydroxyl group is free to interact directly with the adhesin. By isolating
glycosphingolipids from epithelial cells of human stomach from seven
individuals, a binding of H.pylori to the diglycosylceramide region of the
non-acid fraction could be demonstrated in one of these cases. Mass
spectrometry showed that the binding-active sample contained
diglycosylceramides with phytosphingosine and 2-D hydroxy fatty acids with
16-24 carbon atoms in agreement with the results related above.
相似文献
60.
F. Scholz Seyffert Rieger Hagemann G. Szigat H. Polster H. -J. Troll Otto Wettstein Machold Alfred Lein 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1961,31(2):73-76
Ohne Zusammenfassung 相似文献