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1.
The intestinal absorption of glucose- and galactose-conjugated compounds was studied in the everted sac of the rat small intestine. The absorption clearance of p-nitrophenyl beta-D-glucopyranoside (p-NPglc) at 250 microM in the mucosal side (4.45 +/- 0.34 microL/min/cm, mean +/- SE, N = 4), calculated by dividing the absorption rate by the drug concentration, was significantly decreased (0.476 +/- 0.036 microL/min/cm) in the presence of 1 mM phloridzin, an inhibitor of glucose transport, and in the absence of Na+, a cosubstrate of the glucose transport carrier (0.424 +/- 0.018 microL/min/cm). The absorption clearance of p-NPglc was decreased as its concentration increased. In the same experiment, the absorption clearance of p-nitrophenyl beta-D-galactopyranoside (1.99 +/- 0.23 microL/min/cm) was also significantly decreased in the presence of phloridzin and in the absence of Na+. However, the absorption clearance of p-nitrophenyl beta-D-mannopyranoside (0.811 +/- 0.013 microL/min/cm) was low and not significantly decreased in the presence of phloridzin (P greater than 0.1). Furthermore, the absorption clearance of beta-naphthyl beta-D-glucopyranoside and beta-naphthyl beta-D-galactopyranoside was also significantly decreased in the presence of phloridzin (P less than 0.001). These results indicated that the glucose and galactose moieties provided these compounds with a new route by way of the glucose transport carrier for intestinal absorption. 相似文献
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Pharmaceutical Research - 相似文献
3.
Furosemide 1-O-acyl glucuronide (Fgnd) was reversibly bound to a single class of binding sites on human serum albumin (HSA), and the binding of Fgnd decreased with increasing F concentrations, suggesting that Fgnd binds to the same warfarin binding sites on HSA as F binds. The rate of Fgnd degradation (hydrolysis and acyl migration) decreased in the presence of HSA. Although the formation of acyl migration isomers of Fgnd was slower in the presence of HSA than in its absence, hydrolysis of Fgnd to F was faster in the presence of HSA. Rapid minor irreversible binding of Fgnd to HSA within 30 min was followed by slow major irreversible binding. Slow irreversible binding of Fgnd to HSA was decreased by F, though not significantly. This suggests that major irreversible binding may proceed via reversible binding. It has been reported that acyl migration is a prerequisite for irreversible binding. Therefore, these results indicate that HSA decreases irreversible binding of Fgnd to protein by suppressing acyl migration. Furthermore, these results suggest that HSA may prevent irreversible binding of Fgnd to other proteins in the body by decreasing the concentration of reactive Fgnd in the unbound form. HSA eliminates reactive Fgnd by hydrolysis to F. Therefore, it is concluded that HSA works as a scavenger to decrease reactive compounds by reversible binding or eliminates reactive compounds by irreversible binding. 相似文献
4.
Takano H Hasegawa H Narumi H Shindo S Mizuma H Kuwabara Y Kobayashi Y Komuro I 《Journal of human hypertension》2012,26(11):656-663
The Valsartan Amlodipine Randomized Trial (VART) was performed to compare the beneficial effects of valsartan and amlodipine on cardiovascular events in Japanese hypertensive patients. In this subanalysis of the VART, we assessed the relationship between home blood pressure (HBP) levels and cardiovascular events in the enrolled patients. We enrolled 1021 patients with mild-to-moderate hypertension in the VART. The participants were allocated randomly to either the valsartan group or the amlodipine group. The primary end point was a composite of all-cause death, sudden death, cerebrovascular events, cardiac events, vascular events and renal events. A total of 621 patients (valsartan group: 305 and amlodipine group: 316) completed the measurements of HBP (morning and evening) throughout the trial. Both the agents evenly and significantly lowered morning HBP and evening HBP throughout the trial. There was no significant difference in the primary end point between the two groups. However, we observed significant decreases in the left ventricular mass index and urinary albumin to creatinine ratio in the valsartan group but not in the amlodipine group. There were no significant differences in HBP levels and the main outcome of the cardiovascular events between the valsartan and amlodipine groups. However, in the valsartan group, significant improvements in left ventricular hypertrophy and microalbuminuria were observed. 相似文献
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6.
Morikawa Takanori Ishida Masaharu Takadate Tatsuyuki Hata Tatsuo Iseki Masahiro Kawaguchi Kei Ohtsuka Hideo Mizuma Masamichi Hayashi Hiroki Nakagawa Kei Motoi Fuyuhiko Kamei Takashi Naitoh Takeshi Unno Michiaki 《Surgery today》2020,50(2):153-162
Surgery Today - We introduced a superior approach and a unique technique to retract the stomach, called the “stomach roll-up technique”, to standardize laparoscopic distal... 相似文献
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8.
Purpose. To characterize the intestinal absorption of a -glucose conjugate of acyclovir (9-[(2-hydroxyethoxy) methyl] guanine, ACV) and compare it to ACV and its analogues in terms of stability and transport by Na+/glucose cotransporter (SGLT1).
Methods. ACVglc was enzymatically synthesized using cellulase. Intestinal absorption experiments were performed with rat everted small intestine. Conformation of the glucose moiety was analyzed by NMR spectroscopy.
Results. The ACVglc was stable on the mucosal side, and was transported to the serosal side in all regions of the small intestine. However, significant contribution of SGLT1 to the transport of ACVglc was not observed. NMR spectroscopic analysis indicated that the glucose conformation of ACVglc was the 4C1 chair form, identical to (-glucose or SGLT1-transportable -glucosides reported previously. Therefore, other factors such as molecular size and charge due to aglycone may cause no transport of ACVglc by SGLT1. On the other hand, the hydrophilicity of ACVglc was much higher than of ACV, suggesting water solubility-derived improvement of intestinal absorption of ACV.
Conclusions. ACVglc is stable and absorbable, but it is not transported by SGLT1. No involvement of SGLT1 in the ACVglc transport is not due to glucose conformation. 相似文献
9.
Fluorescence energy transfer study of the relationship between the lone tryptophan residue and drug binding sites in human serum albumin 总被引:3,自引:0,他引:3
The relationship between the lone tryptophan residue at position 214 and drug binding sites (Sites I and II) in human serum albumin (HSA) was studied by fluorescence energy transfer. The distance between the lone tryptophan residue and ligands bound to HSA was estimated by F?rster's equation, taking into consideration the degree of ligand binding at these sites, as determined from binding parameters (binding constant, k, and the number of binding sites, n). For all ligands investigated, the distance in each case appeared to asymptotically decrease when the occupation ratio of the binding sites increased with ligand concentration. When the primary binding site of each ligand in HSA was almost saturated, the distance attained a constant value, making possible a somewhat more exact determination of the distance. The distance ranged from approximately 22 to 23 A for ligands typical of Site I (warfarin, dansylamide, dansylglutamine), and approximately 16.1 to 17.5 A for ligands typical of Site II (dansylsarcosine, dansylproline, dansylglycine, diazepam, flufenamic acid). 相似文献
10.
The membrane permeabilities of acetaminophen glucuronide and sulfate produced through conjugative metabolism were examined in isolated rat hepatocytes. The glucuronide formed in hepatocytes was gradually released into the medium and its intracellular level decreased. Release of the sulfate formed in hepatocytes occurred more rapidly and its intracellular level remained almost constant. The permeability of acetaminophen was so rapid that it caused instantaneous equilibrium between hepatocytes and the medium. Its intracellular level thus decreased by conjugation reactions, but compensation for this decrease from the medium was soon made so that a constant intracellular level was resumed. The uptake of both preformed glucuronide and sulfate into hepatocytes indicated carrier-mediated transport. From these results, a pharmacokinetic model is proposed in which conjugative metabolism occurs in two consecutive steps: conjugative reactions of the parent compound taken up instantaneously into hepatocytes and membrane transport of conjugates into the medium. Changes in the amount of acetaminophen, its glucuronide, and its sulfate in the hepatocytes and medium as a function of time simulated according to the model closely agreed with those actually observed. Consequently, membrane permeability of the conjugates was concluded to be essential for conjugative metabolism. 相似文献