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41.
Noë lla Deslauriers Mounia Oudghiri Jacynthe Seguin Luc Trudel 《Immunological investigations》1986,15(4):339-349
In the oral cavity, salivary immunoglobulins (Igs) are the principal mediators of specific immunity. Using carbachol to stimulate saliva flow, we investigated, in a kinetic study, individual variations in salivary Ig concentrations in 23 adult BALB/c mice using an enzyme-linked immuno-sorbant assay (ELISA). It appeared that salivary Ig concentrations are highly variable in individual mice (IgA: 3-81 μg/mL; IgG: 0-2.9 μg/mL; IgM: 0.002-0.14 μg/mL). In individual mice stimulated at different times over a 3 week period there are considerable variations both in salivary Ig concentrations and in their respective ratio. Broad variations were also found in the levels of specific IgA and IgG antibodies to three indigenous oral murine bacteria. Present data thus indicate that among genetically identical mice of the same age and sex, sharing identical diet, there is considerable heterogeneity in salivary Igs. As this heterogeneity was mimicked at the cellular level in major and minor salivary gland-associated B-cells, it appears that antibody dynamics in the oral cavity could reflect the adaptive capacity of the oral immune system to local antigenic challenge. 相似文献
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Matthieu Hanf Catherine Quantin Paddy Farrington Eric Benzenine N. Mounia Hocine Michel Velten Pascale Tubert-Bitter Sylvie Escolano 《Vaccine》2013
In the French national health insurance information system (SNIIR-AM), routine records of health claimed reimbursements are linked to hospital admissions for the whole French population. The main focus of this work is the usability of this system for vaccine safety assessment programme. Self-controlled case series analyses were performed using an exhaustive SNIIR-AM extraction of French children aged less than 3 years, to investigate the relationship between MMR immunization and children hospitalizations for febrile convulsions, a well-documented rare adverse event, over 2009–2010. The results suggest a significant increase of febrile convulsions during the 6–11 days period following any MMR immunization (IRR = 1.49, 95% CI = 1.22, 1.83; p = 0.0001) and no increase 15–35 days post any MMR immunization (IRR = 1.03, 95% CI = 0.89, 1.18; p = 0.72). These results are in accordance with other results obtained from large epidemiologic studies, which suggest the usability of the SNIIR-AM as a relevant database to study the occurrence of adverse events associated with immunization. For future use, results associated with risk of convulsion during the day of vaccination should nevertheless be considered with particular caution. 相似文献
44.
Prokineticins (PK1 and PK2) are peptide hormones that exert their biological activity via two common G-protein-coupled receptors: prokineticin receptor (PKR) 1 and 2. Their physiology was originally explored mostly in the context of angiogenic actions in the reproductive tract and gut motility. Since autocrine and paracrine loops have been established between PK2 and PKR1 in the heart, in this review we focus on the PK2/PKR1 signalling in the functions of the heart and kidney. PKR1 signalling is required for cardiomyocyte survival and angiogenesis. In the mouse model of myocardial infarction, intracardiac transient PKR1 transfection protects the structure and function of the heart. Gain- and loss-of-function studies reveal that PKR1 in mouse heart up-regulates its own ligand and PK2, which in turn acts as a paracrine signal and promotes epicardin-positive progenitor cell differentiation into a vasculogenic cell type. Transgenic mice over-expressing PKR1 in cardiomyocytes exhibit increased neovascularization. Loss of PKR1 causes structural and functional changes in the heart and kidney. In isolated epicardin-positive progenitor cells from the kidney, PK2, acting via PKR1, stimulates differentiation of these progenitor cells into endothelial and smooth muscle cells. Taken together, these data show that PK2/PKR1 is involved in postnatal cardiac and renal neovascularization. The knowledge gained from these studies should facilitate the discovery of therapeutic interventions in heart and kidney diseases targeting PKR1. 相似文献
45.
Sebastián Videla Mounia Lahjou Pascal Guibord Zhengguo Xu Carles Tolrà Gregorio Encina Eric Sicard Artur Sans 《Drugs in R&D》2012,12(4):217-225
Background
Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. The data available on the pharmacokinetic profile of doxylamine in humans are limited, notwithstanding that this drug has been marketed in European countries for more than 50 years. In fact, no data on the effect of food on the pharmacokinetic parameters of doxylamine are available.Objective
The objective of this study was to evaluate the pharmacokinetic parameters of doxylamine following a single oral dose of doxylamine hydrogen succinate 25 mg in healthy human subjects under fed and fasting conditions.Study Design
This was a single-center, randomized, single-dose, laboratory-blinded, two-period, two-sequence, crossover study.Setting
The study was conducted in a phase I clinical unit.Subjects and Methods
A single oral dose of doxylamine hydrogen succinate 25 mg (equivalent to 17.4 mg of doxylamine base) was administered to healthy volunteers under either fed conditions (high-fat, high-calorie food intake) or fasting conditions in each study period. The drug administrations were separated by a wash-out period of seven calendar days. Plasma samples were collected for up to 60 hours postdose, and plasma doxylamine concentrations were determined by a high-performance liquid chromatography method with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs, and 12-lead electrocardiography.Results
In total, 24 healthy subjects (12 male and 12 female) were included in the study. Doxylamine succinate 25 mg tablets exhibited similar oral bioavailability of doxylamine in the fasting state (mean maximum plasma drug concentration [Cmax] 118.21 ng/mL, coefficient of variation [CV] 19.2%; mean area under the plasma concentration time curve from time zero to time t [AUCt] 1746.97 ng · h/mL, CV 31.6%) and in the fed state (mean Cmax 120.99 ng/mL, CV 15.0%; mean AUCt 1712.20 ng · h/mL, CV 26.7%). No statistically significant between-treatment differences were observed for any of the pharmacokinetic parameters under study. The fed: fasting ratios of the geometric least squares means with corresponding 90% confidence intervals for Cmax and AUCt were within the range of 80–125%.Conclusion
High-fat, high-calorie food intake does not affect the kinetics of doxylamine in healthy subjects. The drug was safe and well tolerated by the subjects in this study. 相似文献46.
Sebastián Videla Jesús Cebrecos Mounia Lahjou France Wagner Pascal Guibord Zhengguo Xu Anna Cabot Mercedes Encabo Gregorio Encina Eric Sicard Artur Sans 《Drugs in R&D》2013,13(2):129-135
Background
Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose proportionality of the pharmacokinetics of doxylamine are available, although this drug has been marketed in European countries for more than 50 years.Objective
The objective of this study was to evaluate and compare the dose proportionality between two marketed strengths (12.5 mg and 25 mg) of doxylamine hydrogen succinate after a single oral dose administration under fasting conditions in healthy human subjects.Study Design
This was a single-center, randomized, single dose, laboratory-blinded, two-period, two-sequence, crossover study.Setting
The study was conducted in a phase I clinical unit.Subjects and Methods
A single oral dose of doxylamine hydrogen succinate of 12.5 mg (equivalent to 8.7 mg of doxylamine base) or 25 mg (equivalent to 17.4 mg of doxylamine base) was administered to healthy volunteers under fasting conditions in each study period. The drug administrations were separated by a wash-out period of 7 calendar days. Blood samples were collected for up to 60 h post-dose, and plasma doxylamine levels were determined by an ultra high-performance liquid chromatography method with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using non-compartmental analysis. Dose proportionality was assessed based on the parameter area under the concentration–time curve (AUCt normalized). Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs and 12-lead electrocardiogram (ECG).Results
In total, 12 healthy volunteers (3 male; 9 female) were included in the study. Mean maximum observed plasma concentration (Cmax) and area under the concentration–time curve from time zero to time t (AUCt) of doxylamine hydrogen succinate 12.5 mg and 25 mg tablets increased linearly and dose-dependently [12.5 mg: mean Cmax 61.94 ng/mL, coefficient of variation (CV) 23.2 %; mean AUCt 817.33 ng·h/mL, CV 27.4 %; and 25 mg: mean Cmax 124.91 ng/mL, CV 18.7 %; mean AUCt 1630.85 ng·h/mL, CV 22.8 %]. Mean AUCt normalized was 815.43 ng·h/mL, CV 22.8 % for 25 mg. The dose-normalized geometric mean ratio (%, 12.5 mg/25 mg) of AUCt was 98.92 (90 % CI: 92.46, 105.83). The most common adverse event was somnolence.Conclusions
Exposure to doxylamine was proportional over the therapeutic dose range of 12.5–25 mg in healthy volunteers. Based on the results, a predictable and linear increase in systemic exposure can be expected. Doxylamine hydrogen succinate was safe and well tolerated. 相似文献47.
Adèle Coriati Jenna Sykes Lionelle Nkam Mounia N. Hocine Pierre-Régis Burgel Anne L. Stephenson 《Journal of cystic fibrosis》2019,18(3):396-398
Studies of large CF populations using registry data are important to identify people at high risk for death. Nkam et al. published a prognostic score developed on French CF registry data to predict death or lung transplantation (LT) over a 3-year period in the adult CF population. The goal of our study was to validate the proposed tool using the Canadian CF registry. Using data between 2011 and 2014, a total of 2043 adult CF patients were included. We found that the French prognostic score was a good predictor of death or LT in the Canadian CF population (OR for each unit increase: 3.12, 95% CI: 2.74–3.55; p value < 0.001). The proposed prognostic score accurately categorizes patients when applied to an external dataset. This score provides an important tool for early identification of patients at high risk for death or LT, in whom specific therapeutic intervention can be proposed. 相似文献
48.
49.
Davide Pareyson Tanya Stojkovic Mary M. Reilly Sarah Leonard‐Louis Matilde Laur Julian Blake Yesim Parman Esra Battaloglu Meriem Tazir Mounia Bellatache Nathalie Bonello‐Palot Nicolas Lvy Sabrina Sacconi Raquel Guimares‐Costa Sharham Attarian Philippe Latour Guilhem Sol Andr Megarbane Rita Horvath Giulia Ricci Byung‐Ok Choi Angelo Schenone Chiara Gemelli Alessandro Geroldi Mario Sabatelli Marco Luigetti Lucio Santoro Fiore Manganelli Aldo Quattrone Paola Valentino Tatsufumi Murakami Steven S. Scherer Lois Dankwa Michael E. Shy Chelsea J. Bacon David N. Herrmann Alberto Zambon Irene Tramacere Chiara Pisciotta Stefania Magri Stefano C. Previtali Alessandra Bolino 《Annals of neurology》2019,86(1):55-67
50.
Transient elastography alone and in combination with FibroTest® for the diagnosis of hepatic fibrosis in alcoholic liver disease
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Cosmin Sebastian Voican Alexandre Louvet Jean‐Baptiste Trabut Micheline Njiké‐Nakseu Sébastien Dharancy Andrea Sanchez Marion Corouge Karima Lamouri Amandine Lebrun Axel Balian Sophie Prévot Mounia Lachgar Sophie Maitre Hélène Agostini Philippe Mathurin Gabriel Perlemuter Sylvie Naveau 《Liver international》2017,37(11):1697-1705