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121.
Effect of Adrenocorticotropin Administration on β-Adrenergic Receptor Adaptations in Rat Brain Cerebral Cortex 总被引:1,自引:1,他引:0
Ronald S. Duman Terrance Andree D. A. Kendall S. J. Enna 《Journal of neurochemistry》1984,42(1):33-37
It has been reported that adrenocorticotropin (ACTH) administration reduces the time necessary for observing the imipramine-induced decline in beta-adrenergic receptor binding and function in rat brain frontal cortex. This interaction was examined in the present study following the destruction of the dorsal noradrenergic bundle in an attempt to determine whether the hormone treatment influences pre- or postsynaptic activity to facilitate the receptor response. Lesioning completely prevented the decline in beta-receptor binding normally observed following treatment with the drug combination. In fact, the number of cerebral cortical beta-adrenergic receptor binding sites was significantly greater in lesioned animals receiving ACTH than in lesioned controls. Lesioning significantly increased the amount of cyclic AMP produced in response to a saturating concentration of norepinephrine, an effect that was not influenced by ACTH treatment. These findings suggest that ACTH administration modifies the norepinephrine-stimulated cyclic nucleotide system indirectly, perhaps through an action on presynaptic neurons, whereas the effect on receptor recognition site number may be due to a direct action on the postsynaptic cell. 相似文献
122.
Lipoxygenase mRNA in rabbit reticulocytes. Its isolation, characterization and translational repression 总被引:2,自引:0,他引:2
The synthesis of the erythroid lipoxygenase, an enzyme which is of importance for the degradation of mitochondria during the maturation of reticulocytes to erythrocytes, was studied in reticulocytes from bone marrow and in density-separated fractions from peripheral blood of anemic rabbits. Lipoxygenase mRNA was enriched to about 75% by digestion of polysomes with protease K, poly(U)-Sepharose chromatography and repeated sucrose gradient centrifugation. From sucrose gradient centrifugation, electrophoresis and electron microscopy a molecular weight of about 10(6) was calculated. Synthesis of lipoxygenase is absent in erythroblasts, in very young reticulocytes obtained from bone marrow, or in the lightest fractions of reticulocytes from the peripheral blood. More mature blood reticulocytes show a considerable synthesis of the enzyme. The induction of the synthesis of the lipoxygenase seems to be initiated when reticulocytes have reached the peripheral blood. It is shown that lipoxygenase mRNA is present in reticulocytes as a translationally inactive free cytoplasmic messenger ribonucleoprotein (mRNP) particle. After deproteinization isolated mRNA obtained from masked mRNP codes for authentic lipoxygenase in a cell-free protein-synthesizing system of reticulocytes. 相似文献
123.
124.
Metal ion and substrate binding to bovine galactosyltransferase 总被引:1,自引:0,他引:1
Bovine milk galactosyltransferase was examined by ESR and NMR proton relaxation measurements to determine the stoichiometry and nature of manganese and UDP-Gal substrate binding. The ESR and NMR data clearly showed the binding of two (Mn(II) per mol of enzyme in the ternary complex (enzyme-manganese-UDP-Gal). The affinity of the enzyme for manganese is much higher in the presence of UDP-Gal than in its absence. A deenhancement was observed in both water and UDP-Gal proton relaxation rates upon ternary complex formation [enzyme-Mn(II)-UDP-Gal] relative to the metal-substrate [Mn(II)-UDP-Gal] binary complex, yet the temperature dependence of the water proton relaxation rate was consistent with fast exchange. A simple model was proposed which accounted for the pronounced deenhancement, involving a slow conformational interconversion of an initially formed, rapidly exchanging conformer of the enzyme-Mn(II)-UDP-Gal complex to a second form which contributes negligibly to the relaxation. 相似文献
125.
Zhou D Harrison BL Shah U Andree TH Hornby GA Scerni R Schechter LE Smith DL Sullivan KM Mewshaw RE 《Bioorganic & medicinal chemistry letters》2006,16(5):1338-1341
The design, synthesis, and structure-activity relationship of two novel classes of benzoxazine derivatives with dual selective serotonin reuptake inhibitors and 5-HT(1A) receptor activities are described. 相似文献
126.
R E Mewshaw J A Nelson U S Shah X Shi H Mazandarani J Coupet K Marquis J A Brennan T H Andree 《Bioorganic & medicinal chemistry letters》1999,9(17):2593-2598
The synthesis of several bioisosteric analogs based on the 3-OH-phenoxyethylamine dopamine D2 agonist template (i.e., 3) is described. The benzimidazol-2-ones and benzthioimidazol-2-ones (7-10) and 2-trifluoromethyl-benzimidazole (13) were observed to have excellent affinity for the D2 receptor. 相似文献
127.
Blaukat A Micke P Kalatskaya I Faussner A Müller-Esterl W 《American journal of physiology. Heart and circulatory physiology》2003,284(6):H1909-H1916
Sustained activation of G protein-coupled receptors results in an attenuation of cellular responses, a phenomenon termed desensitization. Whereas mechanisms for rapid desensitization of ligand-receptor-G protein-effector systems are relatively well characterized, much less is known about long-term adaptation processes that occur in the continuous presence of an agonist. Here we have studied the fate of endogenously expressed bradykinin B(2) receptors on human fibroblasts during prolonged agonist treatment. Stimulation with bradykinin for up to 24 h resulted in a 50% reduction of surface binding sites that was paralleled by a similar decrease of total B(2) receptor protein followed by Western blotting using monoclonal antibodies to the B(2) receptor. Whereas B(2) receptor mRNA levels did not change during 24 h of agonist treatment, B(2) receptor de novo synthesis was attenuated by 35-50%, indicating translational control of B(2) receptor levels. Furthermore, the half-life of B(2) receptor protein was shortened by 20-40% as shown by (35)S-labeled pulse-chase and immunoprecipitation experiments. This study demonstrates that bradykinin B(2) receptor expression during long-term agonist treatment is primarily regulated on the (post)translational level, i.e., by attenuation of de novo synthesis and by reduction of receptor stability. 相似文献
128.
Phospholipid regulates the activation of factor X by tissue factor/factor VIIa (TF/VIIa) via substrate and product interactions 总被引:1,自引:0,他引:1
Although the phospholipid requirement for tissue factor (TF) activity has been well-established, the mechanism by which the surface regulates enzymatic activity remains unclear. We added phospholipid vesicles to already relipidated TF (30/70 PS/PC) and found that added lipid can both enhance and inhibit the rate of factor X (F.X) activation. Using active-site-inhibited F.Xa we demonstrate that F.Xa is a more potent inhibitor of TF/VIIa at lower lipid concentrations, and that this inhibition is attributable to high surface occupancy by F.Xa near the enzyme. We also find that exactly twice as many F.Xa molecules are bound to a lipid surface at saturation as F.X, and that a dimer model of F.Xa binding to the lipid can account for the experimentally observed, preferential binding of F.Xa (compared to F.X) to phospholipid surfaces. We manipulated the amount of phospholipid available to each TF molecule by controlling vesicle size and the number of TF molecules per vesicle and found that, as the 2D radius of phospholipid available to each TF molecule was increased, the observed k(cat) increased hyperbolically toward a maximum or "true k(cat)". At a 2D lipid radius of approximately 37 nm, the observed k(cat) was 50% of the "true k(cat)". Thus, phospholipid surface serves as a conduit for F.X presentation and F.Xa removal, and the rate at which F.Xa leaves the vicinity of the enzyme, either by lateral diffusion or desorption from the surface, regulates the rate of F.X activation. We argue that these findings require reevaluation of existing models of coagulation. 相似文献
129.
Basement membrane formation during wound healing is dependent on epidermal transplants 总被引:4,自引:0,他引:4
Andree C Reimer C Page CP Slama J Stark BG Eriksson E 《Plastic and reconstructive surgery》2001,107(1):97-104
The purpose of the study was to compare directly the effect of healing and the formation of the basement membrane during wound healing from two autologous primary keratinocyte cultures in the liquid environment in full-thickness wounds in pigs. Wounds were either transplanted with cultured epidermal autografts (n = 26) or autologous keratinocyte suspensions (n = 24) or treated with saline alone (n = 40) and covered with a chamber. All wounds transplanted with cultured epidermal autografts and keratinocyte cell suspensions had positive "take" after transplantation. Healing times were significantly shorter for wounds treated with either cultured epidermal autografts or keratinocyte suspensions (p = 0.0001) compared with saline-treated wounds but were not different from each other (p = 0.1835). There were no differences in cytokeratin and laminin expression; however, staining with monoclonal antibody against collagen type VII showed a lower signal for cultured epidermal autografts only on days 8 and 16 compared with keratinocyte suspensions. Electron microscope evaluation showed a higher incidence of anchoring fibrils and a more mature dermal-epidermal junction in wounds treated with keratinocyte cell suspensions at day 8. These findings may be due to the single, noncontact-inhibited cells and the early formation of an in vivo neodermis to the wet wound environment. These data suggest that wounds transplanted with autologous keratinocyte suspensions in a wet environment may be an alternative method in the treatment of wounds. 相似文献
130.
Konarska L Skierski J Ellert A Steinbrich J Woźniak A Kalczak M 《Acta biochimica Polonica》2001,48(3):783-793
Currently available data suggest that DNA aneuploidy is associated with aggressive behavior of and unfavorable prognosis in several malignant human tumors as compared with diploid malignancies. However, the diagnostic and prognostic importance of flow cytometric DNA measurements in the case of thyroid neoplasms remains controversial. Therefore, the aim of our study was to evaluate utility of DNA index (DI) and proliferative index (PI) in distinguishing benign from malignant thyroid lesions taking into account the possible influence of intra-tumor heterogeneity and tissue preparation mode on DNA flow-cytometry measurements. A retrospective study was performed on 71 paraffin-embedded specimens from 57 patients with benign and malignant thyroid pathologies: 13 colloid goitres, 12 parenchymatous goitres, 19 adenomas and 13 carcinomas. In 14 of 57 cases two separate specimens taken from different areas of the same lesion were analysed and DNA parameters were compared. Additionally, flow cytometry DNA analysis was parallelly performed on 3 adjacent but differently processed tissue sections (fresh, formalin-fixed and paraffin-embedded) taken from each of 26 surgically excised thyroid lesions. DNA content was also analysed in both fresh and formalin-fixed twin specimens of normal pig thyroid glands (N = 6). We demonstrated that all tumors diagnosed as thyroid carcinomas were associated with abnormal nuclear DNA content although aneuploidy was not found specific to malignant thyroid tumors. Aneuploid samples of benign thyroid lesions exhibited higher proliferative activity, expressed as mean PI values, than diploid ones. In carcinomas the mean PI values were significantly higher than in benign lesions, independently whether they concerned aneuploid or diploid tissues. Considering intra-tumor heterogeneity, the flow cytometric DNA parameters can be assumed as reproducible despite differences in the mode of tissue fixation and preparation for analysis. 相似文献