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排序方式: 共有109条查询结果,搜索用时 31 毫秒
1.
Y. BÖTTIGER P. DOSTERT M. STROLIN BENEDETTI M. BANI F. FIORENTINI M. CASATI I. POGGESTI C. ALM G. ALVAN & L. BERTILSSON 《British journal of clinical pharmacology》1996,42(6):707-711
1 Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia.
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l−1 and AUC (0, t h) 144 nmol l−1 h, mean MDL C max 183 nmol l−1 and AUC 2627 nmol l−1 h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL C max 356 nmol l−1 and AUC 10512 nmol l−1 h, MDL concentrations below limit of quantitation).
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism. 相似文献
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL C
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism. 相似文献
2.
G. SCAMBIA P. BENEDETTI PANICI F. BATTAGLIA G. FERRANDINA C. GAGGINI S MANCUSO 《International journal of gynecological cancer》1991,1(6):253-258
Abstract. Scambia G, Benedetti Panici P, Battaglia F, Ferrandina G, Gaggini C, Mancuso S. Presence of epidermal growth factor (EGF) receptor and proliferative response to EGF in six human ovarian carcinoma cell lines. Int J Gynecol Cancer 1991; 1 : 253–258.
We investigated the role of the EGF-EGFR system as a regulator of ovarian cancer cell growth. In five (OVCA 433, OV 166, OV 1225, OV RS 1000, JA1) of six ovarian cancer cell lines examined we showed the presence of a single high-affinity125 I-EGF binding site with Kd varying from 0.24 to 0.86 nM and a number of binding sites/cell from 9700 to 75 000. In OVCA 433, OV 166, and OV RS 1000 cells we demonstrated a low-affinity 125 I-EGF binding site with Kd ranging from 1.10 to 2.12 nM.
TR-170 cells lacked the EGF binding and were unresponsive to EGF in terms of cell proliferation while all EGFR+ cells except JA 1 exhibited a proliferative response to EGF. Moreover, the growth response of the four EGF-sensitive cell lines showed different patterns since at high EGF concentrations (100 ng ml−1 ) there was no longer a stimulatory effect in OV 1225, OV 166, and OV RS 1000 cells while the mitogenic activity was still present in OVCA 433 cells.
Our results demonstrate that EGF plays a role in regulating ovarian cancer cell growth. However, the presence of EGFR is not a perfect indicator of the EGFR system functionality. The cell lines we have examined could be useful models to clarify the mechanism of EGF action and the role played by the EGF system in the onset and spread of ovarian tumors. 相似文献
We investigated the role of the EGF-EGFR system as a regulator of ovarian cancer cell growth. In five (OVCA 433, OV 166, OV 1225, OV RS 1000, JA1) of six ovarian cancer cell lines examined we showed the presence of a single high-affinity
TR-170 cells lacked the EGF binding and were unresponsive to EGF in terms of cell proliferation while all EGFR+ cells except JA 1 exhibited a proliferative response to EGF. Moreover, the growth response of the four EGF-sensitive cell lines showed different patterns since at high EGF concentrations (100 ng ml
Our results demonstrate that EGF plays a role in regulating ovarian cancer cell growth. However, the presence of EGFR is not a perfect indicator of the EGFR system functionality. The cell lines we have examined could be useful models to clarify the mechanism of EGF action and the role played by the EGF system in the onset and spread of ovarian tumors. 相似文献
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4.
MAURO MARASTONI SEVERO SALVADORI GIANFRANCO BALBONI GIULIANO MARZOLA ETTORE CIRO DEGLIUBERTI ROBERTO TOMATIS 《Chemical biology & drug design》1986,28(3):274-281
Dermorphinoyl(DMR)-glycine, DMR-sarcosine and DMR-glycyl-arginine have been prepared in order to examine the effect of C-terminal extension of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) on opioid activity. On GPI preparation the addition of Gly, Sar, or Gly-Arg to the carboxyl terminus of dermorphinoic acid was detrimental to μ activity: dermorphinoyl-derivatives, in fact, retain only 5–20% of dermorphin potency. Following intracerebroventricular administration (tail-flick test), whereas the analgesic activities of compounds showed the trend dermorphin >DMR-Sar> DMR-Gly-Arg>DMR-Gly>morphine, the nonapeptide displayed highest activity after subcutaneous injection in mice: DMR-Gly-Arg was 2.5 and 10 times more potent than dermorphin and morphine, respectively. 相似文献
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6.
RALPH-HEIKO MATTERN YUSUkE AMINO ETTORE BENEDETTI MURRAY GOODMAN 《Chemical biology & drug design》1997,50(4):286-299
Four potent sweet-tasting molecules, N-(3, 3-dimethylbutyl)-l -aspartyl-l -phenylalanine methylester 1 (7000 times more potent than sucrose), N-(3, 3-dimethylbutyl)-l -aspartyl-d -valine (S)-α-ethylbenzylamide 2 (3000 time more potent than sucrose), l -aspartyl-d -valine (R)-α-methoxymethylbenzylamide 3 (1350 times more potent than sucrose and l -aspartyl-(1R, 2S, 4S)-1-methyl-2-hydroxy-4-phenylhexylamide 4 (2500 times more potent than sucrose) were studied by H NMR and computer simulations. These flexible molecules adopt multiple conformations in solution. The “L-shaped” structure, which we believe to be responsible for sweet taste is accessible to all four compounds in solution. Extended conformations with the AH and B-containing moieties in the +y-axis and the hydrophobic group X pointing in the y-axis have also been observed for all four sweeteners. For compounds 1 and 3 , the solid-state conformations were determined by X-ray diffraction studies. These results demonstrate that compounds 1 and 3 adopt an “L-shaped” structure even in the crystalline state. The extraordinary potency of the N-alkylated compound 1 compared with the unsubstituted Asp-Phe-OMe may be explained by the effect of a second hydrophobic binding domain in addition to interactions arising from the “L-shaped” structure. 相似文献
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9.
ETTORE BENEDETTI ALFONSO BAVOSO BENEDETTO DI BLASIO VINCENZO PAVONE CARLO PEDONE CLAUDIO TONIOLO GIAN MARIA BONORA 《Chemical biology & drug design》1982,20(4):312-319
A conformational analysis of Piv-l-Pro-d-Pro-OMe was performed in the solid state using i.r. absorption and X-ray diffraction. The tertiary amide bond is in the trans conformation, whereas the tertiary peptide bond is in the cis conformation. The sequence of the, ø angles is F, F*. The preferred conformations of the pivaloylamino group, the pyrrolidine rings, and the ester moiety are also discussed. 相似文献
10.
ANTONIO BENEDETTI GIANNA FERRETTI GIOVANNA CURATOLA EUGENIO BRUNELLI ANNE MARIE JÉZÉQUEL FRANCESCO ORLANDI 《Journal of gastroenterology and hepatology》1989,4(3):221-227
The study of membrane fluidity is a rapidly expanding field of research and its interest in hepatology has been stressed recently. The present study is the first report concerned with the determination of membrane fluidity of isolated rat hepatocytes. The data have been compared with those obtained in plasma membrane fractions and subfractions (basolateral or canalicular) derived from homogenates. The fluorescent probes used to measure the fluidity were diphenylhexatriene (DPH) a 'classical' probe, and its derivative trimethylammoniodiphenylhexatriene (TMA-DPH) at 25 degrees C and at 37 degrees C. The values obtained with DPH were lower than those with TMA-DPH, probably due to the localization of the probes in different regions of the phospholipid bilayer. In addition, DPH revealed significant differences in the fluorescence polarization values obtained in isolated hepatocytes compared with membrane fractions, which was in contrast to TMA-DPH, where the respective values were of the same order of magnitude. This behaviour is probably due to the mobility of DPH in the membrane core and its rapid internalization into the cell, whereas TMA-DPH remains anchored for a long time on the cell surface. These findings suggest that TMA-DPH is a better probe than DPH for measuring the fluorescence polarization of whole isolated hepatocytes and that the use of different probes might be of help in exploring different zones of the membrane bilayer. 相似文献