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1.
Chih-Wei Hsu Sheng-Yu Lee Yao-Hsu Yang Liang-Jen Wang 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2020,23(10):653
BackgroundGeneric antidepressants are approved on the market based on evidence of bioequivalence to their brand-name versions. We aimed to assess whether generic antidepressants exert equal effectiveness as their brand-name counterparts for treating patients with depressive disorders.MethodsIn a nationwide, population-based cohort in Taiwan from 1997 through 2013, patients with a diagnosis of a depressive disorder aged between 18 and 65 years who were new users of antidepressant drugs were classified into either the brand-name group or the generic group. All patients were followed up until medication discontinuation or the end of the study period. We assessed the risk for hospitalization as a primary outcome and augmentation therapy, daily dose, medication discontinuation, or switching to another antidepressant as secondary outcomes.ResultsA total of 277 651 brand-name users (35.8% male; mean age: 41.2 years) and 270 583 generic users (35.8% male; mean age: 41.0 years) were divided into 10 different antidepressant groups (fluoxetine, sertraline, paroxetine, escitalopram, citalopram, venlafaxine, mirtazapine, moclobemide, imipramine, and bupropion). We found that patients treated with the generic form of sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine, and bupropion demonstrated significantly higher risks of psychiatric hospitalization (adjusted hazard ratios ranged from 1.20–2.34), compared to their brand-name counterparts. The differences between brand-name antidepressants and their generic counterparts in secondary outcomes varied across different drugs.ConclusionsCompared to most generic antidepressants, brand-name drugs exhibited more protective effects on psychiatric hospitalization for depressive patients. These findings could serve as an important reference for clinicians when encountering patients with depressive disorder. 相似文献
2.
Algorithms based on deep neural networks (DNNs) have attracted increasing attention from the scientific computing community. DNN based algorithms are
easy to implement, natural for nonlinear problems, and have shown great potential to
overcome the curse of dimensionality. In this work, we utilize the multi-scale DNN-based algorithm (MscaleDNN) proposed by Liu, Cai and Xu (2020) to solve multi-scale
elliptic problems with possible nonlinearity, for example, the p-Laplacian problem.
We improve the MscaleDNN algorithm by a smooth and localized activation function.
Several numerical examples of multi-scale elliptic problems with separable or non-separable scales in low-dimensional and high-dimensional Euclidean spaces are used
to demonstrate the effectiveness and accuracy of the MscaleDNN numerical scheme. 相似文献
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Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals. 相似文献
6.
J. Åberg B. Abrahamsson M. Grind G. Nyberg B. Olofsson 《European journal of clinical pharmacology》1997,52(6):471-477
Objective: The primary aim of this study was to investigate whether bioequivalence is achieved for a new fixed combination of extended-release
(ER) felodipine and controlled-release (CR/ZOK) metoprolol␣compared with the free combination of felodipine ER metoprolol
CR/ZOK. The second aim was to study whether there was an interaction in pharmacokinetics and pharmacodynamics between felodipine
and metoprolol when administered as ER formulation.
Methods: Two four-way cross-over studies were performed in 36 young subjects and 24 elderly subjects with frequent measurement of
drug plasma concentrations, blood pressures and heart rate. The pharmacokinetic analysis included enantioselective analysis
in six subjects.
Results: Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%)
except for a minor deviation regarding Cmax of metoprolol in the elderly. No significant interaction was shown except for a small increase (6%) of metoprolol AUC in
the younger subjects. Mean plasma S-/R-enantiomer ratios were almost identical for the different treatments. Blood pressure and heart rate was significantly reduced
for the fixed combination compared with felodipine ER in the younger and the elderly subjects. No significant difference regarding
pharmacodynamics was detected between the fixed combination and the corresponding free combination.
Conclusion: The fixed combination consistently provides fairly constant and effective felodipine and metoprolol concentrations after
once-daily administration of one tablet. It is clinically interchangeable with the free combination of metoprolol CR/ZOK tablets
and felodipine ER tablets. Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered
as the fixed combination.
Received: 29 October 1996 / Accepted in revised form: 21 March 1997 相似文献
7.
Angel J. Amante Herwig-Ulf Meier-Kriesche Linda Schoenberg B. D. Kahan 《Transplant international》1997,10(3):217-222
The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use
for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose
to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations
after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling
from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor
the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly
greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (Cav) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de
novo administration of CyA-ME than with CyA-GC.
Received: 13 September 1996 Accepted: 7 January 1997 相似文献
8.
R. Schall F. O. Müller H. K. L. Hundt L. Duursema G. Groenewoud M. Van Dyk A. M. C. Van Schalkwyk 《Biopharmaceutics & drug disposition》1994,15(6):493-503
Four controlled-release nifedipine products were investigated in two clinical studies. In study 1, 22 healthy male volunteers took part in an open, multiple-dose, randomized, crossover study to determine the relative bioavailablity of two 10 mg controlled-release nifedipine tablet (Adalat® Retard, Bayer), administered 12 hourly, and one 20 mg controlled-release nifedipine tablet (Adalat® Retard, Bayer) administered 12 hourly. In study 2, 24 healthy male volunteers took part in an open, multiple-dose, randomized, three-period, crossover study to determine the relative bioavailability of (i) two 30 mg nifedipine gastro-intestinal therapeutic system (GITS) tablets (Adalat® XL, Bayer) administered once daily; (ii) one 60 mg nifedipine GITS tablet (Adalat® XL, Bayer) administered once daily; and (iii) one 20 mg plus one 10 mg nifedipine controlled-release tablet (Adalat® Retard, Bayer), administered 12 hourly. In both studies detailed pharmacokinetic data, in particular with respect to the controlled-release characteristics of the different formulations, were collected. Results of both studies indicate that all nifedipine products investigated are bioequivalent with respect to the extent of absorption of nifedipine. The nifedipine GITS products (Adalat® XL) have better controlled-release properties than the Adalat® Retard product, and are suitable for once-a-day administration. 相似文献
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10.
Objective: Permeability of basement membrane and all other barriers contains a term for membrane thickness (Δx). This naturally leads to development of methods for measuring Δx that are imprecise, inaccurate, expensive, subject to preparation artifact, and inattentive to variability. Although height and shape of permeability (P) vs. probe radius (α) curves are sensitive to Δx, ln(P) or ln(P/free diffusivity or Do) curves have shapes independent of Δx. It should, thus, be possible using such characteristics to determine fiber radius (rf) and void volume ratio (ε) without Δx. We developed such a method to derive membrane structure by the standard model of Ogston and present its experimental evaluation. Methods: Basement membranes were self-assembled using 1: 1 Matrigel: 0.01 M Tris/150 mM NaCl/1.0 mM CaCl2 buffer on 0.4-μ polycarbonate supports with transport measured in diffusion chambers using FITC-labeled hydroxyethyl starch probes from 25 to 102 Å in radius. Sampling was at 0.5 hr and then for each hour up to 5. Other membranes were measured 7 days after formation. Results: The best fit of the new technique occurred at 3 hr with R2 = 0.949 ± 0.003 SEM, rf = 36.8 ± 2.4 Å, and ε = 0.87 ± 0.02. Membranes studied for 7 days showed more variability but essentially the same characteristics. Conclusions: Membrane thickness is not necessary to reduce permeability of basement membrane to structure, and optimum sampling time is 3 hr. 相似文献