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11.
Expression and characterization of melanin-concentrating hormone receptors on mammalian cell lines 总被引:4,自引:0,他引:4
The neuropeptide melanin-concentrating hormone (MCH) is expressed in central and peripheral tissues where it participates in the complex network regulating energy homeostasis as well as in other physiologically important functions. Two MCH receptor subtypes, MCH-R1 and MCH-R2, have been cloned which signal through activation of Gi/o/q proteins and hence regulate different intracellular signals, such as inhibition of cAMP formation, stimulation of IP3 production, increase in intracellular free Ca2+ and/or activation of MAP kinases. Most of the data were obtained with cell systems heterologously expressing either of the MCH receptors. Fewer reports exist on studies with cell lines which endogenously express MCH receptors. Here, we describe human and other mammalian cell lines with which MCH receptor activation can be studied under "natural" conditions and we summarize the characteristics and signaling pathways of the MCH receptors in the different cell systems. 相似文献
12.
Styczyński J Wysocki M Debski R Kurylak A Balwierz W Rokicka-Milewska R Matysiak M Balcerska A Kowalczyk J Wachowiak J Sońta-Jakimczyk D Chybicka A 《Acta biochimica Polonica》2002,49(1):99-107
Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols. 相似文献
13.
Styczyński J Wysocki M Debski R Balwierz W Rokicka-Milewska R Matysiak M Balcerska A Kowalczyk J Wachowiak J Sońta-Jakimczyk D Chybicka A 《Acta biochimica Polonica》2002,49(1):221-225
Glufosfamide (beta-D-glucosyl-ifosfamide mustard) is a new agent for cancer chemotherapy. Its pharmacology is similar to commonly used oxazaphosphorines, but it does not require activation by hepatic cytochrome P-450 and preclinically demonstrates lower nephrotoxicity and myelosuppression than ifosfamide. The aim of the study was a comparison of the drug resistance profiles of glufosfamide and other oxazaphosphorines in childhood acute leukemias. Leukemic cells, taken from children with ALL on diagnosis (n = 41), ALL on relapse (n = 12) and AML on diagnosis (n = 13) were analyzed by means of the MTT assay. The following drugs were tested: glufosfamide (GLU), 4-HOO-ifosfamide (IFO), 4-HOO-cyclophosphamide (CYC) and mafosfamide cyclohexylamine salt (MAF). In the group of initial ALL samples median cytotoxicity values for GLU, IFO, CYC and MAF were 15.5, 33.8, 15.7 and 7.8 microM, respectively. In comparison with initial ALL samples, the relative resistance for GLU and IFO in relapsed ALL samples was 1.9 (p = 0.049) and 1.3 (ns), and in initial AML samples 31 (p < 0.001) and 5 (p = 0.001), respectively. All oxazaphosphorines presented highly significant cross-resistance. Glufosfamide presented high activity against lymphoblasts both on diagnosis and on relapse. 相似文献
14.
A near infrared spectroscopic method was developed to determine drug content in a 20% (wt/wt) ibuprofen and spray-dried hydous
lactose blend. A blending profile was obtained after blending for 0.5, 1, 3, 5, 10, and 20 minutes. Stream sampling was used
to collect about 20 blend samples at each of the blending times from a laboratory scale V-blender. The samples collected were
used to develop a near infrared calibration model. The calibration model was then used to determine the drug content of unknown
samples from 2 validation blends. The validation blends were not included in the calibration model; they were used to evaluate
the effectiveness of the calibration model. A total of 45 samples from the 2 validation blends were predicted by the near
infrared calibration model and then analyzed by a validated UV spectrophotometric method. The root mean square error of prediction
for the first validation blend was 5.69 mg/g and 3.30 mg/g for the samples from the second blend. A paired t test at the 95%
confidence level did not indicate any differences between the drug content predicted by the near infrared spectroscopy (NIRS)
method and the validated UV method for the 2 blends. The results show that the NIRS method could be developed while the blending
profile is generated and used to thoroughly characterize a new formulation during development by analyzing a large number
of samples. The new formulation could be transferred to a manufacturing plant with an NIRS method to facilitate blend uniformity
analysis. 相似文献
15.
Crocenzi FA Mottino AD Cao J Veggi LM Pozzi EJ Vore M Coleman R Roma MG 《American journal of physiology. Gastrointestinal and liver physiology》2003,285(2):G449-G459
Endocytic internalization of the multidrug resistance-associated protein 2 (Mrp2) was previously suggested to be involved in estradiol-17beta-D-glucuronide (E217G)-induced cholestasis. Here we evaluated in the rat whether a similar phenomenon occurs with the bile salt export pump (Bsep) and the ability of DBcAMP to prevent it. E217G (15 micromol/kg i.v.) impaired bile salt (BS) output and induced Bsep internalization, as assessed by confocal microscopy and Western blotting. Neither cholestasis nor Bsep internalization occurred in TR- rats lacking Mrp2. DBcAMP (20 micromol/kg i.v.) partially prevented the decrease in bile flow and BS output and substantially prevented E217G-induced Bsep internalization. In hepatocyte couplets, E217G (50 microM) diminished canalicular accumulation of a fluorescent BS and decreased Bsep-associated fluorescence in the canalicular membrane; DBcAMP (10 microM) fully prevented both effects. In conclusion, our results suggest that changes in Bsep localization are involved in E217G-induced impairment of bile flow and BS transport and that DBcAMP prevents this effect by stimulating insertion of canalicular transporter-containing vesicles. Mrp2 is required for E217G to induce its harmful effect. 相似文献
16.
W Sinkiewicz A Marzec A Jankowski A Hoffmann K Makuch B Romański 《Polski tygodnik lekarski (Warsaw, Poland : 1960)》1990,45(23-24):458-460
Therapeutical efficacy was clinically evaluated in 21 patients with ventricular cardiac arrhythmias. The drug was given orally with preceded intramuscular dose. Therapeutic effect was verified by the measurements of procainamide and N-acetylprocainamide concentrations in blood serum to determine the minimal effective concentration of the drug required to obtain satisfactory antiarrhythmic effect. Procainamide proved effective in cardiac arrhythmias in 14 patients (66.7%) with statistical significance in the acute myocardial infarctions; blood serum procainamide plus N-acetylprocainamide levels being were below the therapeutical range. The poor correlation of the dose of the drug and respective procainamide, N-acetylprocainamide concentrations in blood was observed. Relationship of the therapeutical effects blood serum level of the drug should be estimated basing of the assays of both procainamide and N-acetylprocainamide . 相似文献
17.
Ilmara Varotto Roma Neto Renan Augusto Ribeiro Mariangela Hungria 《World journal of microbiology & biotechnology》2010,26(7):1291-1302
Biodiversity of diazotrophic symbiotic bacteria in the tropics is a valuable but still poorly studied resource. The objective
of this study was to determine if a second housekeeping gene, glnII, in addition to the 16S rRNA, can be employed to improve the knowledge about taxonomy and phylogeny of rhizobia. Twenty-three
elite rhizobial strains, very effective in fixing nitrogen with twenty-one herbal and woody legumes (including species from
fourteen tribes in the three subfamilies of the family Leguminosae) were selected for this study; all strains are used as commercial inoculants in Brazil. Complete sequences of the 16S rRNA
and partial sequences (480 bp) of the glnII gene were obtained. The same primers and amplification conditions were successful for sequencing the glnII genes of bacteria belonging to five different rhizobial genera—Bradyrhizobium, Mesorhizobium, Methylobacterium, Rhizobium, Sinorhizobium)—positioned in distantly related branches. The analysis of the concatenated genes (16S rRNA + glnII) considerably improved information about phylogeny and taxonomy of rhizobia in comparison to the single analysis of the 16S
rRNA. Nine strains might belong to new species. The complementary analysis of the glnII gene was successful with all strains and improved the phylogenetic clustering and clarified the taxonomic position of several
strains. The strategy of including the analysis of glnII, in addition to the 16S rRNA, is cost- and time- effective for the characterization of large rhizobial culture collections
or in surveys of many isolates. 相似文献
18.
Manuel Olivares Fernando Pizarro Daniel López de Romaña Manuel Ruz 《Biological trace element research》2010,136(2):180-186
To measure the effect of acute copper (Cu) administration, given as an aqueous solution, on the absorption of iron (Fe), 29
healthy adult women participated in two iron absorption studies. Subjects received 0.5 mg of Fe, as ferrous sulfate, alone
or with Cu, as copper sulfate, at 0.5:1, 1:1, or 2:1 Cu/Fe molar ratios (study I) or at 4:1, 6:1, or 8:1 Cu/Fe molar ratios
(study II) as an aqueous solution on days 1, 2, 14, and 15 of the study. Fe absorption was assessed by erythrocyte incorporation
of iron radioisotopes 55Fe and 59Fe. Geometric mean (range ± SD) absorption of Fe alone or at 0.5:1, 1:1, 2:1 Cu/Fe molar ratios were 34.4% (17.3–68.5%), 40.9%
(24.9–67.2%), 48.3% (24.8–94.1%), and 50.2% (25.3–99.5%), respectively (ANOVA, p = 0.12). Geometric mean (range ± SD) absorption of Fe alone or at 4:1, 6:1, 8:1 Cu/Fe molar ratios were 28.7% (12.1–67.9%),
21.5% (6.5–71.5%), 29.6% (10.3–85.4%), and 36.5% (18.3–73.1%), respectively (ANOVA, p = 0.16). In conclusion, combined Cu and Fe administration in an aqueous solution does not inhibit Fe bioavailability. This
information could help in the design of rational guidelines for copper and iron supplementation programs. Our results support
the hypothesis that divalent metal transporter 1 is not physiologically relevant for copper absorption in humans. 相似文献
19.
Malaria remains a major health burden especially for the developing countries. Despite concerted efforts at using the current control tools, such as bed nets, anti malarial drugs and vector control measures, the disease is accountable for close to a million deaths annually. Vaccines have been proposed as a necessary addition to the armamentarium that could work towards elimination and eventual eradication of malaria in view of their historical significance in combating infectious diseases. However, because malaria vaccines would work differently depending on the targeted parasite stage, this review addresses the potential impact various malaria vaccine types could have on transmission. Further, because of the wide variation in the epidemiology of malaria across the endemic regions, this paper proposes that the ideal approach to malaria control ought to be tailor-made depending on the specific context. Finally, it suggests that although it is highly desirable to anticipate and aim for malaria elimination and eventual eradication, many affected regions should prioritize reduction of mortality and morbidity before aspiring for elimination. 相似文献
20.
Gonzalez MA Alvarez Mdel L Pisani GB Bernal CA Roma MG Carrillo MC 《Biological trace element research》2007,116(3):329-348
We have shown that aluminum (Al) induces cholestasis associated with multiple alterations in hepatocellular transporters involved
in bile secretory function, like Mrp2. This work aims to investigate whether these harmful effects are mediated by the oxidative
stress caused by the metal. For this purpose, the capability of the antioxidant agent, vitamin E, to counteract these alterations
was studied in male Wistar rats. Aluminum hydroxide (or saline in controls) was administered ip (27 mg/kg body weight, three
times a week, for 90 d). Vitamin E (600 mg/kg body weight) was coadministered, sc. Al increased lipid peroxidation (+50%)
and decreased hepatic glutation levels (-43%) and the activity of glutation peroxidase (-50%) and catalase (-88%). Vitamin
E counteracted these effects total or partially. Both plasma and hepatic Al levels reached at the end of the treatment were
significantly reduced by vitamin E (-40% and -44%, respectively;p< 0.05). Al increased 4 times the hepatic apoptotic index, and this effect was fully counteracted by vitamin E. Bile flow
was decreased in Al-treated rats (-37%) and restored to normality by vitamin E. The antioxidant normalized the hepatic handling
of the Mrp2 substrates, rose bengal, and dinitrophenyl-S-glutathione, which was causally associated with restoration of Mrp2
expression. Our data indicate that oxidative stress has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage,
and the impairment in liver transport function induced by Al and that vitamin E counteracts these harmful effects not only
by preventing free-radical formation but also by favoring Al disposal. 相似文献