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461.
Oxidation-induced misfolding and aggregation of superoxide dismutase and its implications for amyotrophic lateral sclerosis 总被引:6,自引:0,他引:6
Rakhit R Cunningham P Furtos-Matei A Dahan S Qi XF Crow JP Cashman NR Kondejewski LH Chakrabartty A 《The Journal of biological chemistry》2002,277(49):47551-47556
The presence of intracellular aggregates that contain Cu/Zn superoxide dismutase (SOD1) in spinal cord motor neurons is a pathological hallmark of amyotrophic lateral sclerosis (ALS). Although SOD1 is abundant in all cells, its half-life in motor neurons far exceeds that in any other cell type. On the basis of the premise that the long half-life of the protein increases the potential for oxidative damage, we investigated the effects of oxidation on misfolding/aggregation of SOD1 and ALS-associated SOD1 mutants. Zinc-deficient wild-type SOD1 and SOD1 mutants were extremely prone to form visible aggregates upon oxidation as compared with wild-type holo-protein. Oxidation of select histidine residues that bind metals in the active site mediates SOD1 aggregation. Our results provide a plausible model to explain the accumulation of SOD1 aggregates in motor neurons affected in ALS. 相似文献
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463.
Price D Drago G Noble J Simmons R Crow S Ahearn D 《Journal of industrial microbiology & biotechnology》2002,29(6):368-372
A membrane-screening method was developed in conjunction with flow cytometric (FC) analysis for determining the efficacies
of antimould pressure-treatment formulations for mould species of cosmetic significance on southern pine. Fusarium subglutinans, Aspergillus flavus, Penicillium chrysogenum, and Paecilomyces spp. were the predominant moulds colonizing surfaces of the variously treated pine stored in sealed plastic bags over 3-
to 6-month periods. Nylon membranes placed directly on pressure-treated pine and membranes saturated with the various formulations
were inoculated with the conidia of selected moulds. FC analysis of conidia stained with propidium iodide (PI) before and
after exposure to the pressure-treatment formulations permitted a rapid assessment of the inocula and selection of those pressure-treatment
formulations with probable inhibitory activity versus probable nonactive preparations. Recoveries of the fungi from the membranes
over 9–14 days were in general agreement with the emergence of colonizing fungi on the similarly preserved uninoculated pine
stored in sealed plastic bags for 6 months. This combination of procedures provided for a relatively rapid assessment of preservative
formulations designed to provide enhanced efficacy against surface mould growth on lumber during storage and retail display.
Received 21 December 2001/ Accepted in revised form 20 May 2002 相似文献
464.
Apoptosis repressor with caspase recruitment domain (ARC) is expressed in cancer cells and localizes to nuclei 总被引:4,自引:0,他引:4
Apoptosis repressor with caspase recruitment domain is expressed at high levels in brain and myogenic tissues, consistent with a role to inhibit apoptosis in the terminally differentiated cells. Expression of ARC in cancers is not known. In this study, we reported that ARC was highly expressed in various non-myogenic and non-neurogenic human and rat cancer cell lines. Unexpectedly, ARC was localized almost exclusively to the nuclei of cancer cells, which was unlike the cytoplasmic localization of ARC in non-cancer cells. Furthermore, nuclear ARC in cancer cells did not co-localize with nucleolus protein of 30 kDa, an alternatively spliced ARC isoform. These findings indicate that ARC is distributed differently in cancer cells than non-cancer cells and thus might play a role in neoplastic transformation. 相似文献
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466.
Crow T Xue-Bian JJ Dash PK Tian LM 《Biochemical and biophysical research communications》2004,323(2):395-401
Rho GTPases acting through effector proteins regulate actin dynamics and cytoskeletal structure. In Hermissenda Csp24 is a cytoskeletal-related protein that contributes to the development of intermediate-term memory, and is homologous to other beta-thymosin-like repeat proteins containing multiple actin-binding domains. We have examined the role of Rho GTPase activity and its downstream target ROCK, and cyclin-dependent kinase 5 (Cdk5) on the phosphorylation of Csp24 using 32PO4 labeling of proteins separated with 2-D PAGE. The ROCK inhibitor Y-27632 significantly increased Csp24 phosphorylation, and the Rho activator lysophosphatidic acid (LPA) or the Cdk5 inhibitor butyrolactone significantly decreased Csp24 phosphorylation. Pretreatment with Y-27632 before LPA application significantly reduced the decreased phosphorylation of Csp24 normally detected in nervous systems exposed to LPA. Using a pull-down assay we found that LPA treatments activated Rho and exposure to 5-HT decreased Rho activity. Our results indicate that the Rho/ROCK and Cdk5 signaling pathways contribute to the regulation of Csp24 phosphorylation. 相似文献
467.
Karunakaran C Zhang H Crow JP Antholine WE Kalyanaraman B 《The Journal of biological chemistry》2004,279(31):32534-32540
Using X-band electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) spectroscopy at liquid helium temperatures, the Cu(II) coordination geometry at the active site of bovine and human copper,zinc-superoxide dismutases (bSOD1 and hSOD1) treated with H(2)O(2) and bicarbonate (HCO(3)(-)) was examined. The time course EPR of wild type human SOD1 (WT hSOD1), W32F hSOD1 mutant (tryptophan 32 substituted with phenylalanine), and bSOD1 treated with H(2)O(2) and HCO(3)(-) shows an initial reduction of active site Cu(II) to Cu(I) followed by its oxidation back to Cu(II) in the presence of H(2)O(2). However, HCO(3)(-) induced a Trp-32-derived radical from WT hSOD1 but not from bSOD1. The mutation of Trp-32 by phenylalanine totally eliminated the Trp-32 radical signal generated from W32F hSOD1 treated with HCO(3)(-) and H(2)O(2). Further characterization of the free radical was performed by UV irradiation of WT hSOD1 and bSOD1 that generated tryptophanyl and tyrosyl radicals. Both proton ((1)H) and nitrogen ((14)N) ENDOR studies of bSOD1 and hSOD1 in the presence of H(2)O(2) revealed a change in the geometry of His-46 (or His-44) and His-48 (or His-46) coordinated to Cu(II) at the active site of WT hSOD1 and bSOD1, respectively. However, in the presence of HCO(3)(-) and H(2)O(2), both (1)H and (14)N ENDOR spectra were almost identical to those derived from native bSOD1. We conclude that HCO(3)(-)-derived oxidant does not alter significantly the Cu(II) active site geometry and histidine coordination to Cu(II) in SOD1 as does H(2)O(2) alone; however, the oxidant derived from HCO(3)(-) (i.e. carbonate anion radical) reacts with surface-associated Trp-32 in hSOD1 to form the corresponding radical. 相似文献
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470.
Pattison L Crow YJ Deeble VJ Jackson AP Jafri H Rashid Y Roberts E Woods CG 《American journal of human genetics》2000,67(6):1578-1580
Primary microcephaly is a genetic disorder in which an affected individual has a head circumference >3 SDs below the age- and sex-related mean. A small but apparently normally formed brain is the reason for the reduced head circumference, and, probably because of this, all affected individuals are mentally retarded. The condition is genetically heterogeneous, and four loci have already been identified. We now report a fifth locus, MCPH5, which is an 8-cM region mapping to chromosome 1q31, defined by the markers GATA135F02 and D1S1678. 相似文献