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1.
Tc-99m HMPAO labeled leukocytes superior to bone scan in the detection of osteomyelitis in children.
Seven children (aged 7 to 16 years) with confirmed osteomyelitis underwent imaging with Tc-99m HMPAO labeled leukocytes and with Tc-99m diphosphonates. The patients were scanned at 1/2 hour and at 3 hours. The scans were evaluated visually, and the lesion-to-normal bone ratios were quantitated. All the lesions on leukocyte scans and six out of seven lesions in bone scans were readily detectable 1/2 hour after injection of the radiopharmaceutical, but 3 hours is the better imaging time. In quantitative analysis, the lesion-to-normal bone ratio increased with leukocytes significantly higher than with the bone scans (P less than 0.05). When the scintigraphic findings were compared with surgical and radiologic results, the leukocyte images detected and localized lesions better than the bone scans. According to these preliminary results, Tc-99m HMPAO labeled leukocytes seem to offer a rapid and accurate method for detecting bone infections. 相似文献
2.
K.-M. Kaukonen K. T. Olkkola P. J. Neuvonen 《European journal of clinical pharmacology》1998,53(6):445-449
Objective: Losartan is metabolised to its active metabolite E-3174 by CYP2C9 and CYP3A4 in vitro. Itraconazole is an inhibitor of CYP3A4,
whereas fluconazole affects CYP2C9 more than CYP3A4. We wanted to study the possible interaction of these antimycotics with
losartan in healthy volunteers.
Methods: A randomised, double-blind, three-phase crossover study design was used. Eleven healthy volunteers ingested orally, once
a day for 4 days, either itraconazole 200 mg, fluconazole (400 mg on day 1 and 200 mg on days 2–4) or placebo (control). On
day 4, a single 50-mg oral dose of losartan was ingested. Plasma concentrations of losartan, E-3174, itraconazole, hydroxy-itraconazole
and fluconazole were determined over 24 h. The blood pressure and heart rate were also recorded over 24 h.
Results: The mean peak plasma concentration (Cmax) and area under the curve [AUC(0∞)] of E-3174 were significantly decreased by fluconazole to 30% and to 47% of their control
values, respectively, and the t1/2 was increased to 167%. Fluconazole caused only a nonsignificant increase (23–41%) in the AUC and t1/2 of the unchanged losartan. Itraconazole had no significant effect on the pharmacokinetic variables of losartan or E-3174.
The ratio AUC(0∞)E-3174/AUC(0∞)losartan was 60% smaller during the fluconazole than during the placebo and itraconazole phases. No clinically significant changes
in the effects of losartan on blood pressure and heart rate were observed between fluconazole, itraconazole and placebo phases.
Conclusion: Fluconazole but not itraconazole interacts with losartan by inhibiting its metabolism to the active metabolite E-3174. This
implicates that, in man, CYP2C9 is a major enzyme for the formation of E-3174 from losartan. The clinical significance of
the fluconazole–losartan interaction is unclear, but the possibility of a decreased therapeutic effect of losartan should
be kept in mind.
Received: 4 June 1997 / Accepted in revised form: 10 September 1997 相似文献
3.
Maija Koljonen Kati S Hakala Tuula Ahtola-S?til? Leena Laitinen Risto Kostiainen Tapio Kotiaho Ann Marie Kaukonen Jouni Hirvonen 《European journal of pharmaceutics and biopharmaceutics》2006,64(3):379-387
The purpose of this study was to investigate the suitability and reliability of n-in-one approach using FDA suggested compounds for standardising Caco-2 permeability experiments. Special attention was paid to the evaluation of rank order correlation and mechanistic insights of compound permeability. Transport studies with antipyrine, metoprolol, ketoprofen, verapamil, hydrochlorothiazide, ranitidine, mannitol and fluorescein were performed in 12- and 24-well formats, as single compounds and in cocktails under iso-pH 7.4 and pH-gradient (pH 5.5 vs. 7.4) conditions. Compounds were quantified using n-in-one LC/MS/MS analysis. The cocktail-dosing proved to be a feasible method to determine the permeability of the Caco-2 cell line and to introduce external standards for permeability tests. Even though sink conditions were lost in cocktail experiments for highly permeable compounds, the rank order of compound permeability and the classification to low and high permeability compounds remained unchanged between single and cocktail studies and permeability values of 12- and 24-well formats were directly comparable. Under pH-gradient conditions the margin between high and low permeability compounds was narrower due to the lower permeability (higher fraction of ionisation) of basic molecules. Of the compounds studied, antipyrine, metoprolol, hydrochlorothiazide and mannitol are suitable for evaluation and standardisation purposes of passive permeability, while fluorescein would function as paracellular marker under iso-pH 7.4. As efflux activity may vary between cell batches, verapamil is a useful marker for P-glycoprotein. 相似文献
4.
Porter CJ Kaukonen AM Taillardat-Bertschinger A Boyd BJ O'Connor JM Edwards GA Charman WN 《Journal of pharmaceutical sciences》2004,93(5):1110-1121
The relative oral bioavailability (BA) of halofantrine base (Hf) was assessed in male beagle dogs after administration of a medium chain triglyceride (MCT), a long chain triglyceride (LCT), and a blended LCT/MCT lipid solution formulation of Hf (Study 1) and after administration of suspensions of Hf base and Hf. HCl in LCT (Study 2). A series of in vitro lipid digestion experiments were also performed in an attempt to clarify the data obtained. In vitro drug solubilization profiles were markedly dependent on the mass of lipid employed in lipid digestion experiments. At high lipid masses ( approximately 25 mg triglyceride/mL), MCT formulations gave maximal benefit, whereas at low lipid concentrations ( approximately 5 mg triglyceride/mL), LCT formulations provided improved solubilization capacity. The in vitro digestion and solubilization data at lower lipid masses were consistent with the in vivo data where the BA of Hf after oral administration of the LCT solution > LCT/MCT blend > MCT solution. The second BA study showed similar, albeit variable, exposure after oral administration of a suspension of Hf base or Hf. HCl in LCT and this trend was broadly consistent with in vitro results. This study demonstrates the potential utility of in vitro digestion models to assess and rank order the in vivo performance of lipid solution and suspension formulations of poorly water-soluble drugs such as Hf. 相似文献
5.
Simple end-to-end suture versus augmented repair in acute Achilles tendon ruptures: a retrospective comparison in 98 patients 总被引:5,自引:0,他引:5
Nyyssönen T Saarikoski H Kaukonen JP Lüthje P Hakovirta H 《Acta orthopaedica Scandinavica》2003,74(2):206-208
We retrospectively compared the results in 98 patients with an acute Achilles tendon rupture treated with an augmented tendon repair (n = 59) to patients with an end-to-end suture (n = 39) after an average follow-up of 44 (22-69) months. 7 patients were operated on more than 2 weeks after the rupture, all with augmention. The complication rates in the augmention group were 0.1 and in the end-to-end suture group 0.2. We found no differences in subjective outcome or rerupture rate between the groups. In the augmentation group, the rate of complications was higher in those operated on after 2 weeks than in those operated on before. A simple end-to-end suture seems sufficient. 相似文献
6.
Diseases caused by nuclear genes affecting mtDNA stability 总被引:10,自引:0,他引:10
Diseases caused by nuclear genes that affect mitochondrial DNA (mtDNA) stability are an interesting group of mitochondrial disorders, involving both cellular genomes. In these disorders, a primary nuclear gene defect causes secondary mtDNA loss or deletion formation, which leads to tissue dysfunction. Therefore, the diseases clinically resemble those caused by mtDNA mutations, but follow a Mendelian inheritance pattern. Several clinical entities associated with multiple mtDNA deletions have been characterized, the most frequently described being autosomal dominant progressive external ophthalmoplegia (adPEO). MtDNA depletion syndrome (MDS) is a severe disease of childhood, in which tissue-specific loss of mtDNA is seen. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients may have multiple mtDNA deletions and/or mtDNA depletion. Recent reports of thymidine phosphorylase mutations in MNGIE and adenine nucleotide translocator mutations in adPEO have given new insights into the mechanisms of mtDNA maintenance in mammals. The common mechanism underlying both of these gene defects could be disturbed mitochondrial nucleoside pools, the building blocks of mtDNA. Future studies on MNGIE and adPEO pathogenesis, and identification of additional gene defects in adPEO and MDS will provide further understanding about the mammalian mtDNA maintenance and the crosstalk between the nuclear and mitochondrial genomes. 相似文献
7.
Alvik's glenoplasty for humeroscapular dislocation. 6-year follow-up of 52 shoulders 总被引:1,自引:0,他引:1
In Alvik's modification of the Eden-Hybbinette operation, an iliac crest bone graft is inserted in a groove in the glenoid rim of the scapula. In this retrospective study, 52 shoulders in 46 patients operated on using the modified Alvik's method were reviewed. The mean age of the patients at the time of the operation was 32 years, and the average follow-up time was 6 years. There were no operative complications, and two thirds of the patients were satisfied with the operation. Spontaneous redislocation occurred postoperatively in only one shoulder. In addition, there were 10 traumatic redislocations. Postoperative arthrosis was found in nine shoulders; the arthrosis had more correlation with the patient's age at the time of the operation than with the follow-up time. In 41 shoulders, there was bony healing of the transplant. 相似文献
8.
Julius Sipil Harri Nurmi Ann Marie Kaukonen Jouni Hirvonen Jyrki Taskinen Jari Yli-Kauhaluoma 《European journal of pharmaceutical sciences》2005,25(4-5):417-425
Currently there are several compounds used as drugs or studied as new chemical entities, which have an electron withdrawing group connected to a vinylic double bond in a phenolic or catecholic core structure. These compounds share a common feature – current computational methods utilizing the Hammett type equation for the prediction of ionisation constants fail to give accurate prediction of pKa's for compounds containing the vinylic moiety. The hypothesis was that the effect of electron-withdrawing substituents on the pKa of p-vinyl phenols is due to the delocalized electronic structure of these compounds. Thus, this effect should be additive for multiple substituents attached to the vinylic double bond and quantifiable by LFER-based methods. The aim of this study was to produce an improved equation with a reduced tendency to underestimate the effect of the double bond on the ionisation of the phenolic hydroxyl. To this end a set of 19 para-substituted vinyl phenols was used. The ionisation constants were measured potentiometrically, and a training set of 10 compounds was selected to build a regression model (r2 = 0.987 and S.E. = 0.09). The average error with an external test set of six compounds was 0.19 for our model and 1.27 for the ACD-labs 7.0. Thus, we have been able to significantly improve the existing model for prediction of the ionisation constants of substituted p-vinyl phenols. 相似文献
9.
Sanna Siissalo Laura Laine Ari Tolonen Ann M. Kaukonen Moshe Finel Jouni Hirvonen 《International journal of pharmaceutics》2010,383(1-2):24-29
The human intestinal cell line, Caco-2, was used to study compounds – indomethacin, paracetamol and 1-naphthol – that undergo intestinal phase II metabolism followed by apical and/or basolateral efflux of the metabolites and/or parent compounds. The interplay was studied during permeability experiments across fully differentiated Caco-2 cell monolayers. The parent compounds and their glucuronide and/or sulfate metabolites were detected by LC–MS/MS. Conjugation of the model compounds and effluxes of their metabolites were observed. The efflux of indomethacin glucuronide was apical, but complementary basolateral efflux was observed at the highest indomethacin concentration (500 μM), probably due to apical saturation. Paracetamol glucuronide was not formed in these experiments, but apical and basolateral effluxes of paracetamol sulfate were observed. A typical bell-shaped inhibition curve was observed for the formation of 1-naphthol glucuronides, indicating substrate or product inhibition of the UGT enzyme(s) at higher 1-naphthol concentrations (200 μM and 500 μM). Based on these results, the fully differentiated Caco-2 cell monolayers can be applied as a platform for qualitative in vitro studies, where phase II metabolism and efflux activities are ongoing simultaneously. 相似文献
10.
Meri Poukkanen Juha Koskenkari Suvi T Vaara Ville Pettil? Sari Karlsson Anna-Maija Korhonen Jouko J Laurila Kirsi-Maija Kaukonen Vesa Lund Tero I Ala-Kokko 《Critical care (London, England)》2014,18(1):R26