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71.
72.
Gaetan Lesca Nadia Boutry‐Kryza Bertrand De Toffol Mathieu Milh Dominique Steschenko Martine Lemesle‐Martin Louis Maillard Giovanni Foletti Gabrielle Rudolf Jørgen Erik Nielsen Bjarke á Rogvi‐Hansen Jesper Erdal Josette Mancini Christel Thauvin‐Robinet Amel M’Rrabet Dorothée Ville Pierre Szepetowski Emmanuel Raffo Edouard Hirsch Philippe Ryvlin Alain Calender Pierre Genton 《Epilepsia》2010,51(9):1691-1698
Purpose: Lafora disease (LD) is an autosomal recessive form of progressive myoclonus epilepsy with onset in childhood or adolescence and with fatal outcome caused by mutations in two genes: EPM2A and NHLRC1. The aim of this study was to characterize the mutation spectrum in a cohort of unrelated patients with presumed LD. Methods: Sequencing of the two genes and search for large rearrangements was performed in 46 unrelated patients with suspected LD, 33 originating from France and the others from different countries. Patients were classified into two groups according to the clinical presentation. Results: Mutations of various types were found in EPM2A in 10 patients and in NHLRC1 in 4 patients. Mutations were found in 14 (93%) of 15 patients with classical clinical and electroencephalography (EEG) presentation of LD and in no patients with an atypical presentation. Ten mutations were novel, including the first substitution reported in a donor splice site of EPM2A, leading to the deletion of exon 2 at the RNA level. Four large deletions, including two deletions of exon 2 with different sizes and breakpoints, were found in EPM2A, corresponding to 20% of the alleles of this gene. Discussion: We described several novel mutations of EPM2A and NHLRC1 and brought additional data to the genetic epidemiology of LD. This study emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy. 相似文献
73.
74.
Loquai C Schmidtmann I Beutel M Sunderkötter C Grabbe S Schiller M Nashan D 《European journal of dermatology : EJD》2011,21(6):976-984
Treatment of malignant melanoma with IFN-α has been associated with significant side-effects. The aim of this retrospective monocentric non-randomized study was first to evaluate the impact on quality of life (QOL) in 30 melanoma patients treated with once weekly 2?μg/kg PEG-IFN-α2b for 18 months, and second to examine whether there is a difference in patients' and physicians' perception of QOL. Data on QOL were collected by means of the EORTC QLQ-C30 questionnaire completed by the patient before consultation at baseline and every three months during treatment. A second questionnaire was filled out independently by the physician, based on the consultation and patient file. All data were routinely collected in an outpatient care unit. At baseline, patients had more favorable mean values on almost all dimensions of the EORTC QLQ-C30 than follow-up assessments. In comparison to published low-dose IFN-α2a data, once weekly 2?μg/kg PEG-IFN-α2b was associated with stronger impairment in most QOL single dimensions but with almost no differences regarding the global health status. QOL documented by physicians was significantly higher than QOL from the patients' questionnaires in all QOL dimensions (p<0.05). PEG-IFN-α2b has measurable effects on QOL. Measuring QOL based only on physicians' patient files without explicitly determining patients' assessments leads to a profound underestimation of impairment of QOL. 相似文献
75.
Avi Saskin Leanne de Kock Nelly Sabbaghian Maria Apellaniz‐Ruiz Ceyhun Bozkurt Dorothée Bouron‐Dal Soglio William D. Foulkes 《Pediatric blood & cancer》2018,65(1)
DICER1 syndrome is an inherited disorder associated with at least a dozen rare, mainly pediatric‐onset tumors. Its characterization remains incomplete. Some studies suggested that neuroblastoma (NB) may be involved in this syndrome. Here, we describe the case of a 14‐year‐old female presenting with a multinodular goiter (MNG) and a collision tumor composed of NB and cystic nephroma (CN). She is a carrier of a deleterious germline mutation in exon 23 of DICER1 and harbored different somatic mutations in the CN and MNG. However, no second hit was found in the NB, questioning its status as a DICER1‐related tumor. 相似文献
76.
Angela?Rosenbohm Raphael?S.?Peter Siegfried?Erhardt Dorothée?Lulé Dietrich?Rothenbacher Albert?C.?LudolphEmail author Gabriele?Nagel The ALS Registry Study Group 《Journal of neurology》2017,264(4):749-757
The objective of this study is to determine the current distribution of clinical phenotypes and to estimate future trends of ALS incidence in Western societies. We report on a clinical-epidemiological registry with a capture–recapture rate of >80% and population-based case–control study in ALS patients in South Western Germany. 1163 incidents of ALS were registered. Clinical and neuropsychological data were prospectively collected from 699 cases. The mean age at onset was 66.6 (SD = 11.6) years in prospective cases (N = 699). The site of onset was more frequently bulbar (34.1%) than lumbosacral (30.7%), cervical (27.0%), or thoracic (3.1%). Cognitive deficits (ranging from 27.5 to 42.1%, depending on the screening instrument) and behavioral changes (29%) were frequently detected. The incidence rate dropped markedly after 79 years of age, and bulbar onset as well as cognitive impairment were more frequent in ALS cases >75 years. The mean survival time of ALS cases from first paresis was 31 months. The age-standardized incidence rate (ASR) of ALS in 2012/2013 was found to be 2.4 (95% CI 2.2–2.7) per 100,000 person-years (resulting in an ASR of 3.1/100,000 with 100% coverage). Based on the predicted age distribution of the German population, the incidence of ALS was estimated to be 4.5/100,000 for men and 3.3/100,000 for women in the year 2050. ALS prevalence will rise to about 9.2–9.8/100,000 person-years in Germany in 2050. An increased proportion of patients with bulbar onset and/or cognitive deficits can be used as basic epidemiologic data on ALS for future health care decisions. 相似文献
77.
Géraldine M. Ferron Yang Dai Dorothée Semiond 《Cancer chemotherapy and pharmacology》2013,71(3):681-692
Purpose
To develop a population pharmacokinetic (PK) model for cabazitaxel in patients with advanced solid tumors and examine the influence of demographic and baseline parameters.Methods
One hundred and seventy patients who received cabazitaxel (10–30 mg/m2, 1-h IV infusion) every 7 or 21 days in five Phase I–III studies were analyzed by non-linear mixed-effect modeling (NONMEM VI). Model evaluation comprised non-parametric bootstrap and visual predictive checks.Results
Cabazitaxel PK was best described by a linear three-compartment model with: first-order elimination; interindividual variability on clearance (CL), central volume of distribution (V1), and all intercompartmental rate constants except K21; interoccasion variability in CL and V1; proportional residual error of 27.8 %. Cabazitaxel CL was related to body surface area (BSA) and tumor type (breast cancer; finding confounded by study). Typical CL for a non-breast cancer patient with a BSA of 1.84 m2 was 48.5 L/h, with V1 26.0 L, steady-state volume of distribution 4,870 L and alpha, beta, and gamma half-lives of 4.4 min, 1.6, and 95 h, respectively. Sex, height, weight, age, Caucasian race, renal/hepatic function, and cytochrome P450 inducer use did not significantly further explain the PK of cabazitaxel. Bootstrap and posterior predictive checks confirmed the adequacy of the model.Conclusions
Cabazitaxel PK appears unaffected by most baseline patient factors, and the influence of BSA on CL is addressed in practice by BSA-dependent doses. This analysis suggests consistent cabazitaxel PK and exposure across most solid tumor types, although the potential influence of breast cancer on CL requires further confirmation. 相似文献78.
Pierre Maison-Blanche Shaker Dakhil Ari Baron Sylvie Rottey Fred Millard Gedske Daugaard Jean-Pascal Machiels William Conkright Sunil Sharma Patricia M. M. B. Soetekouw Jeffrey Yachnin Lisa Sengeløv Peter Van Veldhuizen Sanjiv S. Agarwala Dorothée Sémiond Mustapha Chadjaa Liji Shen James L. Wade 《Cancer chemotherapy and pharmacology》2014,73(6):1241-1252
Purpose
This study assessed the cardiovascular safety of cabazitaxel, based on thorough evaluation of QT and non-QT variables, and the relationship between pharmacokinetic and pharmacodynamic electrocardiographic (ECG) profiles and the occurrence of Grade ≥3 cardiovascular adverse events.Methods
Patients with advanced solid tumors were treated with cabazitaxel 25 mg/m2 every 3 weeks. Digital ECG recordings were obtained during Cycle 1 over 24 h after dosing. The primary end point was effect of cabazitaxel on QT interval corrected by the Fridericia formula (QTcF). Secondary end points were additional ECG parameters (QT, PR and QRS intervals, and heart rate), plasma pharmacokinetics of cabazitaxel and overall clinical safety.Results
The pharmacodynamic (ECG) population included 94 patients. In 63 patients with a full 24-h ECG evaluation, the maximum upper bound of 90 % confidence interval (CI) for mean QTcF change from baseline was 7.46 ms (mean 4.8 ms), occurring at 1 h 30 min post-infusion. The slope of QTcF change from baseline versus cabazitaxel concentration was slightly negative (?0.012 [95 % CI ?0.017; ?0.008], equivalent to a 1.2 ms decrease per 100 ng/mL increase in cabazitaxel concentration). For non-QT variables, no effect was noted. No Grade ≥3 cardiac adverse events were observed; Grade ≥3 hypotension and lymphocele occurred in two patients and one patient, respectively.Conclusion
These results suggest that cabazitaxel has no clinically significant cardiovascular adverse effects in patients with advanced solid tumors. 相似文献79.
The prevalence and characterization of migraine triggers have not been rigorously studied in children and adolescents. Using
a questionnaire, we retrospectively studied the prevalence of 15 predefined trigger factors in a clinic-based population.
In 102 children and adolescents fulfilling the Second Edition of The International Headache Classification criteria for paediatric
migraine, at least one migraine trigger was reported by the patient and/or was the parents’ interpretation in 100% of patients.
The mean number of migraine triggers reported per subject was 7. Mean time elapsed between exposure to a trigger factor and
attack onset was comprised between 0 and 3 h in 88 patients (86%). The most common individual trigger was stress (75.5% of
patients), followed by lack of sleep (69.6%), warm climate (68.6%) and video games (64.7%). Stress was also the most frequently
reported migraine trigger always associated with attacks (24.5%). In conclusion, trigger factors were frequently reported
by children and adolescents with migraine and stress was the most frequent. 相似文献
80.
Kasteleijn-Nolst Trenité D Rubboli G Hirsch E Martins da Silva A Seri S Wilkins A Parra J Covanis A Elia M Capovilla G Stephani U Harding G 《Epilepsia》2012,53(1):16-24
Intermittent photic stimulation (IPS) is a common procedure performed in the electroencephalography (EEG) laboratory in children and adults to detect abnormal epileptogenic sensitivity to flickering light (i.e., photosensitivity). In practice, substantial variability in outcome is anecdotally found due to the many different methods used per laboratory and country. We believe that standardization of procedure, based on scientific and clinical data, should permit reproducible identification and quantification of photosensitivity. We hope that the use of our new algorithm will help in standardizing the IPS procedure, which in turn may more clearly identify and assist monitoring of patients with epilepsy and photosensitivity. Our algorithm goes far beyond that published in 1999 (Epilepsia, 1999a, 40, 75; Neurophysiol Clin, 1999b, 29, 318): it has substantially increased content, detailing technical and logistical aspects of IPS testing and the rationale for many of the steps in the IPS procedure. Furthermore, our latest algorithm incorporates the consensus of repeated scientific meetings of European experts in this field over a period of 6 years with feedback from general neurologists and epileptologists to improve its validity and utility. Accordingly, our European group has provided herein updated algorithms for two different levels of methodology: (1) requirements for defining photosensitivity in patients and in family members of known photosensitive patients and (2) requirements for tailored studies in patients with a clear history of visually induced seizures or complaints, and in those already known to be photosensitive. 相似文献