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101.
The purpose of this study was to mechanistically interpret the oral absorption pattern of trospium in fasted and fed states by means of gastrointestinal simulation technology. A drug absorption model was built on the basis of experimental data. According to the generated model, low permeability across the intestinal epithelium, delayed gastric emptying time and a prolonged residence time in the small intestine are the key factors governing trospium absorption in the fasted state. Furthermore, in silico modelling provided a plausible explanation of the pronounced reduction in the oral bioavailability of trospium when administered with food. The simulation results support the decreased dissolution in viscous medium, and the reduced drug permeability in the fed state as the predominant mechanisms for the food effect on trospium absorption. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
102.
I Adamchic PA Tass B Langguth C Hauptmann M Koller M Schecklmann F Zeman M Landgrebe 《Health and quality of life outcomes》2012,10(1):79
ABSTRACT: BACKGROUND: Development of new tinnitus treatments requires prospective placebo-controlled randomized trials to prove their efficacy. The Tinnitus Questionnaire (TQ) is a validated and commonly used instrument for assessment of tinnitus severity and has been used in many clinical studies. Defining the Minimal Clinically Important Difference (MCID) for TQ changes is an important step to a better interpretation of the clinical relevance of changes observed in clinical trials. In this study we aimed to estimate the minimum change of the TQ score that could be considered clinically relevant. METHODS: 757 patients with chronic tinnitus were pooled from the TRI database and the RESET study. An anchor-based approach using the Clinical Global Impression (CGI) scale and distributional approaches were used to estimate MCID. Receiver Operating Characteristic (ROC) curves were calculated to define optimal TQ change cutoffs discriminating between minimally changed and unchanged subjects. RESULTS: The relationship between TQ change scores and CGI ratings of change was good (r=0.52, p<0.05). Mean change scores associated with minimally better and minimally worse CGI categories were -6.65 and +2.72 respectively. According to the ROC method MCID for improvement was -5 points and for deterioration +1 points. CONCLUSION: Distribution and anchor-based methods yielded comparable results in identifying MCIDs. DeltaTQ scores of -5 and +1 points were identified as the minimal clinically relevant change for improvement and worsening respectively. The asymmetry of the MCIDs for improvement and worsening may be related to expectation effects. METHODS: 757 patients with chronic tinnitus were pooled from the TRI database and the RESET study. An anchor-based approach using the Clinical Global Impression (CGI) scale and distributional approaches were used to estimate MCID. Receiver Operating Characteristic (ROC) curves were calculated to define optimal TQ change cutoffs discriminating between minimally changed and unchanged subjects. RESULTS: The relationship between TQ change scores and CGI ratings of change was good (r=0.43, p<0.05). Mean change scores associated with minimally better and minimally worse CGI categories were -5.6 and +1.2 respectively. According to the ROC method MCID for improvement was -5 points and for deterioration +1 points. CONCLUSION: Distribution and anchor-based methods yielded comparable results in identifying MCIDs. DeltaTQ scores of -5 and +1 points were identified as the minimal clinically relevant change for improvement and worsening respectively. The asymmetry of the MCIDs for improvement and worsening may be related to expectation effects. 相似文献
103.
104.
Elmar Frank Peter Eichhammer Julia Burger Marc Zowe Michael Landgrebe Göran Hajak Berthold Langguth 《European archives of psychiatry and clinical neuroscience》2011,261(4):261-266
An increasing number of controlled studies strongly support an antidepressant effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex. However, these data come from highly selected study populations. Whether rTMS is a feasible therapeutic tool for the treatment of depression under naturalistic condition has not yet been addressed. Here, we report results from 232 depressive patients [aged 20–76 years, baseline Hamilton Depression Rating Score (HDRS-21) 24.0 ± 7.3] treated with rTMS add-on to continued psychopharmacological treatment in a naturalistic clinical setting. Two thousand stimuli of 20-Hz rTMS were applied daily over the left dorsolateral prefrontal cortex with an intensity of 110% of motor threshold. Treatment duration was individually planned and varied between 10 and 20 sessions. In average, patients received 13 ± 6.1 rTMS sessions. In 90% of the cases, treatment was terminated regularly. No severe side effects were observed. Only four patients stopped rTMS treatment because of side effects. Ratings with the HDRS-21 before and after treatment were available in 130 patients. The average improvement of the HDRS-21 in this subsample was 9.0 ± 9.2 points. Fifty-three patients had an improvement of 50% or more. These results document that rTMS is feasible, safe and well tolerated under naturalistic conditions. 相似文献
105.
Gogoll K Stein P Wei H Schild H Radsak M Langguth P 《Biopharmaceutics & drug disposition》2012,33(4):218-228
This work evaluates the transcutaneous in vitro and in vivo immunization efficacy of five commercially available 5% imiquimod containing formulations. The parameters included microscopic analysis, rheological properties, drug permeation across synthetic membranes of molecular weight cutoff 10 kDa and ablated murine skin with both 0.1 m HCl and a phthalate buffer pH 3.6 Ph.Eur./methanol 3/7 (v/v) as receiver solutions in a Franz‐diffusion cell model. For in vivo formulation characterization, the cytotoxic T‐cell activity and interferon‐γ production in C57BL/6 mice was determined ex vivo 24 h after transcutaneous administration. OVA257?264 (SIINFEKL) from chicken albumin served as a target antigen. Microscopic images demonstrated differences with respect to the presence or absence of crystalline API. Rheological properties point to a roughly ten‐fold difference between the products at low shear rates. With regard to drug permeation across synthetic membranes, only ‘Nan Bo’ demonstrated equality compared with Aldara?, resulting in f1 and f2 values of 5.25 and 59.58, respectively. The drug permeation rates were maximum from Aldara? across ablated murine skin. Furthermore, differentiation between the formulations containing crystalline and dissolved states of active imiquimod was possible using this model. The in vivo results yielded significant immunomodulating activities (p < 0.05) of multisource formulations compared with the untreated control group, however, the significance of differences between the formulations was dependent on the parameter of interest. A correlation plot of skin permeation versus in vivo immunostimulating activity yielded a slope significantly different from zero only in the case of the murine skin setup (r between 0.421 and 0.669). Yet this correlation is deemed not satisfactory for formulation optimization. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
106.
Anna Langguth Kansuda Leelahapongsathon Napasaporn Wannapong Suwicha Kasemsuwan Steffen Ortmann Ad Vos Michael Ber 《Viruses》2021,13(7)
Oral vaccination of dogs against rabies has the potential to achieve mass coverage and thus deplete the virus of its most important reservoir host species. There is, however, no established non-invasive method to evaluate vaccine release in the oral cavity, following bait ingestion. In this study, two pre-selected marker methods in conjunction with their acceptance were assessed in local Thai dogs. Shelter dogs (n = 47) were offered one of four randomized bait formulations; bait type A-, containing Green S (E142) in a fructose solution; type B-, containing Patent Blue V (E131) in a fructose solution; type C-, containing the medium used for delivery of oral rabies vaccine in baits commercially produced; and type D-, containing denatonium benzoate, which was to serve as the negative control, due to its perceived bitterness. Patent Blue V was found to possess overall stronger dyeing capacities compared to Green S. Furthermore, there was no significant difference in the acceptance or bait handling of Patent Blue V baits compared to those containing the oral rabies vaccine medium alone, suggesting the potential use of this dye as a surrogate for rabies vaccine when testing newly developed bait formats. 相似文献
107.
108.
Schecklmann M Landgrebe M Frank E Sand PG Eichhammer P Hajak G Langguth B 《International journal of psychophysiology》2012,83(3):323-327
In a previous study an association has been reported between motor cortex excitability, as measured by paired-pulse transcranial magnetic stimulation (TMS) and neuroticism of the NEO personality inventory; this correlation was carried by the men. The aim of the present study was to replicate these findings in a larger sample and with additional measures of motor cortex excitability. Eighty-nine healthy volunteers filled in the NEO-FFI and underwent several measures of motor cortex excitability (resting and active motor thresholds, double-pulse TMS with interstimulus intervals of 1-20ms, and cortical silent period). We did not find any systematic significant correlations of personality factors with motor cortex excitability. Dividing the samples by sex or controlling for confounders such as age, sex and education level by partial correlations did not reveal any significant associations either. Reasons for the failure of replication may include differences in sample characteristics, personality measures, and TMS methodology. However, synopsis of literature indicates that association of personality and motor cortex excitability might be mediated rather by state than by trait factors. 相似文献
109.
目的 基于网络药理学研究预测参附注射液治疗心肌缺血再灌注损伤的主要活性成分、作用靶标和相关信号通路,并应用体外实验验证,揭示参附注射液治疗心肌缺血再灌注损伤潜在作用机制.方法 应用中药系统药理学数据库与分析平台收集参附注射液的有效活性成分和靶点信息;在GeneCards疾病数据和DisGeNET疾病数据库中收集缺血再灌... 相似文献
110.
The flow of bile secretion into the human digestive system was simulated by the dilution of a bile salt-lipid micellar solution. The structural development upon the dilution of the fed state bile model FeSSIF(mod6.5) to the fasted state bile model FaSSIF(mod) was investigated by small-angle neutron scattering (SANS) and dynamic light scattering (DLS) in crossed beam experiments to observe small and large structures in a size range of 1 nm to 50 μm in parallel. Because of the physiologically low lipid and surfactant concentrations of 2.625 mM egg-phosphatidylcholine and 10.5 mM taurocholate the sensitivity of the neutron-structural investigations was improved by partial solvent deuteration with 71% D(2)O, with control experiments in H(2)O. Static experiments of initial and end state systems after 6 days of development revealed the presence of mixed bile salt-lipid micelles of 5.1 nm size in the initial state model FeSSIF(mod6.5), and large liposomes in FaSSIF(mod), which represent the late status after dilution of bile secretion in the intestine in the fasted state. The liposomes depicted a size of 34.39 nm with a membrane thickness of 4.75 nm, which indicates medium to large size unilamellar vesicles. Crossed beam experiments with time-resolved neutron and light scattering experiments after fast mixing with a stopped-flow device revealed a stepwise structural dynamics upon dilution by a factor of 3.5. The liposome formation was almost complete five minutes after bile dilution. The liposomes 30 min after dilution resembled the liposomes found after 6 days and depicted a size of 44.56 nm. In the time regime between 3 and 100 s a kinetic intermediate was observed. In a further experiment the liposome formation was abolished when the dilution was conducted with a surfactant solution containing sodium dodecyl sulfate. 相似文献