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71.
Ping Wang Kenji Abe Tomoko Ojima Junko H. Ohyashiki Hitoshi Satoh Tokumi Maruyama Hiroshi Nagata Hiroshi Tanaka Kohtaro Yamamoto 《Microbiology and immunology》2001,45(6):457-466
An infection of TaY cells, which originated from an adult T-cell leukemia, with an HHV-6B OK isolate resulted in a chronically infected culture, termed TaY(OK). Cell cloning analysis revealed that the TaY(OK) culture consisted of a mixture of cells permissive and refractory to the infection, and that the permissive cells were continuously produced from the refractory cell population. Since the chronically infected culture has been maintained for over 2 years without the addition of uninfected TaY cells, we used it for an evaluation of the antiviral potency of nucleoside analogs, especially carbocyclic oxetanocins (COXTs). MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays showed a lack of toxicity of ganciclovir (GCV), COXTs, and their derivatives, to TaY(OK) cells at 1 μm . Therefore we compared the antiviral potencies of these drugs at 1 μm by monitoring the viral loads produced during a 1-day period during the course of the drug treatment. Among the drugs tested, 3′-fluorocarbocyclic oxetanocin A (3′-C.OXT-A) was the most effective for inhibiting the virus production, and at concentrations ranging from 0.5 μm to 10 μm , the inhibition of the viral production was dose-dependent. A comparison of the chemical structures of the derivatives with that of C.OXT-A, which is the parental molecule, suggested that the 3′-fluorine-modification might account for the higher anti-HHV-6 activity and lower cytotoxicity. 相似文献
72.
Calcium-binding of synaptosomes isolated from rat brain cortex 总被引:2,自引:0,他引:2
73.
Toshiaki Fujihashi Takahiro Ogata Tetsuo Ohkuma Tohru Endo Akira Kaji 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):295-310
Abstract A new cyclic AMP analogue, adenosine- 3′, 5′-cyclic methyl phosphonate (cAMP-Me) was chemically synthesized. This compound was not a substrate for phosphodiesterase, and it did not activate cAMP-dependent protein kinases (type I or type II). However, it inhibited cAMP phosphodiesterase and protein kinase at milimolar concentration levels. It also inhibited malignant cell proliferation in vitro. 相似文献
74.
Hiroshi Habe Shun Sato Tomotake Morita Tokuma Fukuoka Kohtaro Kirimura Dai Kitamoto 《Bioscience, biotechnology, and biochemistry》2013,77(9):1552-1555
Nineteen levulinic acid (LA)-utilizing bacteria were isolated from environmental samples. Following examination of the use of 80 g/L LA by some isolated strains, Brevibacterium epidermidis LA39–2 consumed 62.6 g/L LA following 8 days incubation. The strain also utilized both 90 and 100 g/L LA, with consumption ratio of 84.3 and 53.3%, respectively, after 10 days incubation. 相似文献
75.
Sasaki D Fujihashi M Iwata Y Murakami M Yoshimura T Hemmi H Miki K 《Journal of molecular biology》2011,409(4):543-557
The crystal structure of geranylgeranyl reductase (GGR) from Sulfolobus acidocaldarius was determined in order to elucidate the molecular mechanism of the catalytic reaction. The enzyme is a flavoprotein and is involved in saturation of the double bonds on the isoprenoid moiety of archaeal membranes. The structure determined in this study belongs to the p-hydroxybenzoate hydroxylase family in the glutathione reductase superfamily. GGR functions as a monomer and is divided into the FAD-binding, catalytic and C-terminal domains. The catalytic domain has a large cavity surrounded by a characteristic YxWxFPx7-8GxG motif and by the isoalloxazine ring of an FAD molecule. The cavity holds a lipid molecule, which is probably derived from Escherichia coli cells used for over-expression. One of the two forms of the structure clarifies the presence of an anion pocket holding a pyrophosphate molecule, which might anchor the phosphate head of the natural ligands. Mutational analysis supports the suggestion that the three aromatic residues of the YxWxFPx7-8GxG motif hold the ligand in the appropriate position for reduction. Cys47, which is widely conserved in GGRs, is located at the si-side of the isoalloxazine ring of FAD and is shown by mutational analysis to be involved in catalysis. The catalytic cycle, including the FAD reducing factor binding site, is proposed on the basis of the detailed analysis of the structure. 相似文献
76.
Kino K Kuratsu S Noguchi A Kokubo M Nakazawa Y Arai T Yagasaki M Kirimura K 《Biochemical and biophysical research communications》2007,352(2):351-359
Glutathione (GSH) is synthesized by gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GS) in living organisms. Recently, bifunctional fusion protein, termed gamma-GCS-GS catalyzing both gamma-GCS and GS reactions from gram-positive firmicutes Streptococcus agalactiae, has been reported. We revealed that in the gamma-GCS activity, S. agalactiae gamma-GCS-GS had different substrate specificities from those of Escherichia coli gamma-GCS. Furthermore, S. agalactiae gamma-GCS-GS synthesized several kinds of gamma-glutamyltripeptide, gamma-Glu-X(aa)-Gly, from free three amino acids. In Clostridium acetobutylicum, the genes encoding gamma-GCS and putative GS were found to be immediately adjacent by BLAST search, and had amino acid sequence homology with S. agalactiae gamma-GCS-GS, respectively. We confirmed that the proteins expressed from each gene showed gamma-GCS and GS activity, respectively. C. acetobutylicum GS had broad substrate specificities and synthesized several kinds of gamma-glutamyltripeptide, gamma-Glu-Cys-X(aa). Whereas the substrate specificities of gamma-GCS domain protein and GS domain protein of S. agalactiae gamma-GCS-GS were the same as those of S. agalactiae gamma-GCS-GS. 相似文献
77.
Immunohistochemical characterization of cell types expressing the cellular prion protein in the small intestine of cattle and mice 总被引:3,自引:2,他引:1
Miyazawa K Kanaya T Tanaka S Takakura I Watanabe K Ohwada S Kitazawa H Rose MT Sakaguchi S Katamine S Yamaguchi T Aso H 《Histochemistry and cell biology》2007,127(3):291-301
The gastrointestinal tract is thought to be the main site of entry for the pathological isoform of the prion protein (PrPSc). Prion diseases are believed to result from a conformational change of the cellular prion protein (PrPc) to PrPSc. Therefore, PrPc expression is a prerequisite for the infection and spread of the disease to the central nervous system. However, the distribution
of PrPc in the gut is still a matter of controversy. We therefore investigated the localization of PrPc in the bovine and murine small intestine. In cattle, most PrPc positive epithelial cells were detected in the duodenum, while a few positive cells were found in the jejunum. PrPc was expressed in serotonin producing cells. In bovine Peyer’s patches, PrPc was distributed in extrafollicular areas, but not in the germinal centre of the jejunum and ileum. PrPc was expressed in myeloid lineage cells such as myeloid dendritic cells and macrophages. In mice, PrPc was expressed in some epithelial cells throughout the small intestine as well as in cells such as follicular dendritic cell
in the germinal centre of Peyer’s patches. In this study, we demonstrate that there are a number of differences in the localization
of PrPc between the murine and bovine small intestines. 相似文献
78.
The tobacco hornworm Manduca sexta, like many holometabolous insects, makes two versions of its thoracic legs. The simple legs of the larva are formed during embryogenesis, but then are transformed into the more complex adult legs at metamorphosis. To elucidate the molecular patterning mechanism underlying this biphasic development, we examined the expression patterns of five genes known to be involved in patterning the proximal-distal axis in insect legs. In the developing larval leg of Manduca, the early patterning genes Distal-less and Extradenticle are already expressed in patterns comparable to the adult legs of other insects. In contrast, Bric-a-brac and dachshund are expressed in patterns similar to transient patterns observed during early stages of leg development in Drosophila. During metamorphosis of the leg, the two genes finally develop mature expression patterns. Our results are consistent with the hypothesis that the larval leg morphology is produced by a transient arrest in the conserved adult leg patterning process in insects. In addition, we find that, during the adult leg development, some cells in the leg express the patterning genes de novo suggesting that the remodeling of the leg involves changes in the patterning gene regulation. 相似文献
79.
Although pancreatic exocrine acinar cells have the potential to transdifferentiate into pancreatic endocrine cells, the mechanisms are poorly understood. Here we report that intracellular signaling pathways, including those involving MAPK and phosphatidylinositol 3 (PI3)-kinase, are activated by enzymatic dissociation of pancreatic acinar cells and that spherical cell clusters are formed by cadherin-mediated cell-cell adhesion during transdifferentiation. Inhibition of PI3-kinase by LY294002 prevents spheroid formation by degrading E-cadherin and beta-catenin, blocking transdifferentiation into insulin-secreting cells. In addition, neutralizing antibody against E-cadherin suppresses the induction of genes characteristic of pancreatic beta-cells. We also show that loss of cadherin-mediated cell-cell adhesion induces and maintains a dedifferentiated state in isolated pancreatic acinar cells. Thus, disruption and remodeling of cadherin-mediated cell-cell adhesion is critical in pancreatic exocrine-to-endocrine transdifferentiation, in which the PI3-kinase pathway plays an essential role. 相似文献
80.
Kurusu S Matsui K Watanabe T Tsunou T Kawaminami M 《Cellular and molecular neurobiology》2008,28(8):1109-1118
This study characterized the phospholipase A2 (PLA2) activity in cerebral cortex of fetal rat brain and investigated effects of chemical inhibition of Ca2+-independent PLA2 (iPLA2) on neurite outgrowth and cell development of cortical neurons in vitro. The PLA2 activity in fetal brain was insensitive to a Ca2+-chelator EGTA and was significantly impaired by an iPLA2 inhibitor, bromoenol lactone (BEL). Following treatment with BEL, cortical neurons showed acute loss of neurites and impaired
cell body, which were clearly dose- and time-dependent. Nuclear staining revealed nuclear regression (shrinkage), but not
fragmentation, in BEL-treated cells. The cytotoxic effect of BEL was additive with arachidonic acid (AA) and AA alone also
induced neurite demise. BEL treatment resulted in increased production of prostaglandin E2. Overall data suggest that iPLA2, a primary PLA2 isoform in cerebral cortex, displays a housekeeping role in development and neurite outgrowth in cortical neurons in vitro
probably via maintaining phospholipid membrane remodeling rather than generating free fatty acids and lysophospholipids. 相似文献