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81.
We studied the central representation of pudendal afferents arising from the clitoral nerves in 15 healthy adult female subjects using electrical dorsal clitoral nerve stimulation and fMRI. As a control body region, we electrically stimulated the right hallux in eight subjects. In a block design experiment, we applied bilateral clitoral stimulation and unilateral (right) hallux stimulation. Activation maps were calculated for the contrasts ‘electrical dorsal clitoral nerve stimulation versus rest’ and ‘electrical hallux stimulation versus rest’.A random-effect group analysis for the clitoral stimulation showed significant activations bilateral in the superior and inferior frontal gyri, insulae and putamen and in the postcentral, precentral and inferior parietal gyri (including the primary and secondary somatosensory cortices). No activation was found on the mesial surface of the postcentral gyrus. For the hallux, activations occurred in a similar neuronal network but the activation in the primary somatosensory cortex was localized in the inter-hemispheric fissure.The results of this study demonstrate that the central representation of pudendal afferents arising from the clitoral nerves and sensory inputs from the hallux can be studied and distinguished from each other by fMRI. From the somatotopic order described in the somatosensory homunculus one would expect for electrical clitoral nerve stimulation activation of the mesial wall of the postcentral gyrus. In contrast, we found activations on the lateral surface of the postcentral gyrus. 相似文献
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The influence of diethylstilbestrol (DES) on the SCE frequency was studied in various cell systems (V79, HTC, DON, WI-38, human lymphocytes) differing in their ability to metabolize the two promutagens benzo(a)pyrene and cyclophosphamide as well as after incubation with exogenous metabolic systems (S9 mix and peroxidase/H2O2) and in vivo on cells from the bone marrow of the Chinese hamster. DES concentrations from 10(-6) to 10(-4) M were tested. Slight SCE induction was observed only at the highest concentration (10(-4) M) of DES in human lymphocytes treated with DES for the entire culture period of 72 h and in DON cells. No increase of the SCE rate was determined in the other cell lines and in vivo. The combination with S9 mix or peroxidase/H2O2 also had no influence on the SCE frequency. These findings cast doubt on the assumption that DES is metabolized to a DNA-damaging compound subsequently leading to SCE induction. The positive findings in the SCE test are more likely to be products of an indirect and rather unspecific effect. 相似文献
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Michael E. Hurwitz Paul Markowski Xiaopan Yao Hari Deshpande Jaymin Patel Amir Mortazavi Alessia Donadio Mark N. Stein William Kevin Kelly Daniel Peter Petrylak Janice M. Mehnert 《Clinical genitourinary cancer》2018,16(6):437-444.e6
Background
Sorafenib, an oral tyrosine kinase inhibitor, may enhance the antitumor activity of platinum-based chemotherapy in transitional-cell carcinoma. This study investigated the safety and clinical outcome of adding sorafenib to gemcitabine and carboplatin for patients with advanced transitional-cell carcinoma.Patients and Methods
Subjects with metastatic or unresectable chemotherapy-naive TCC with Eastern Cooperative Oncology Group performance status 0 or 1 received gemcitabine (1000 mg/m2 on days 1 and 8) and carboplatin (area under the curve of 5 on day 1) with sorafenib (400 mg 2 times a day on days 2-19 every 21 days) for 6 cycles. Subjects with stable disease or partial or complete response continued to receive sorafenib until disease progression. The primary end point was progression-free survival (PFS) at 5 months with a secondary end point of response (partial or complete).Results
Seventeen subjects were enrolled. The median number of cycles of gemcitabine and carboplatin with sorafenib provided was 4.4. A total of 15, 5, and 8 subjects required reductions of gemcitabine, carboplatin, and sorafenib, respectively. Thirteen subjects (76%) required multiple dose reductions. Eleven subjects (65%) were free of progression at 5 months. The overall response rate was 54% (95% confidence interval [CI], 0.28-077), with 4 patients experiencing complete response (24%; 95% CI, 0.07-0.50) and 5 partial response (29%; 95% CI, 0.10-0.56); 7 subjects (41%) had stable disease. Median PFS was 9.5 months (95% CI, 0.43-1.26), and median overall survival was 25.2 months (95% CI, 0.96-5.65). One-year PFS was 31%, and 1-year overall survival was 72%. Eleven subjects (65%) discontinued treatment because of toxicity. There were no toxic deaths.Conclusion
Gemcitabine and carboplatin with sorafenib showed clinical activity in advanced TCC, with some prolonged progression-free intervals. However, gemcitabine and carboplatin with sorafenib was associated with significant toxicity, causing discontinuation of therapy in most patients. 相似文献86.
Heide Götze Sabine Taubenheim Andreas Dietz Florian Lordick Anja Mehnert 《Journal of cancer survivorship》2018,12(5):712-720
Purpose
Our study provides a detailed overview of comorbid conditions and health-related quality of life of long-term cancer survivors and analyses the impact of demographic, disease- and treatment-related characteristics.Methods
We present data obtained from 1000 survivors across mixed tumour entities 5 and 10 years after cancer diagnosis in a cross-sectional study. We analyse the prevalence of physical symptoms and health conditions via self-report and health-related quality of life using the EORTC QLQ-C30 in comparison to gender- and age-matched reference values of the general population.Results
Cancer survivors reported on average 5 comorbidities; 23% had 7 or more comorbid conditions. Cancer survivors reported higher physical symptom burden than the population—especially fatigue, insomnia and pain. Type and prevalence of long-term and late effects differ with disease-related factors (e.g. cancer type, treatment) and characteristics of the patient. Cancer survivors also reported lower quality of life than the population, especially in everyday activities, social life, psychological well-being and financial difficulties. There was a positive association between high quality of life and a low level of morbidity.Conclusions
The specific knowledge about physical long-term consequences for the individual types of cancer could raise awareness in health care professionals for high-risk patients and help to develop adequate prevention and survivorship-programs.Implications for Cancer survivors
Limitations in the mental health area underlines the importance of psycho-oncological survivorship-care-plans, which go beyond the time of rehabilitation. Special attention should be given to the financial situation of patients in long-term follow-up care.87.
Cytotoxicity of Solid Lipid Nanoparticles as a Function of the Lipid Matrix and the Surfactant 总被引:7,自引:0,他引:7
Müller Rainer H. Rühl Dörte Runge Stephan Schulze-Forster Kai Mehnert Wolfgang 《Pharmaceutical research》1997,14(4):458-462
Purpose. Assessment of the in vitro cytotoxicity of solid lipid nanoparticles (SLNs) as a function of lipid matrix (Dynasan 114, Compritol ATO 888), and stabilizing surfactant (poloxamers, Tween 80, soya lecithin, and sodium dodecyl sulphate). Comparison with other colloidal carriers should determine their potential use in the clinic.
Methods. SLNs were produced by high pressure homogenisation. Cytotoxicity was assessed by measuring the viability of HL60 cells and human granulocytes after incubation with SLNs. Particle internalisation was quantified by chemiluminescence measurements.
Results. The nature of the lipid had no effect on viability; distinct differences were found for the surfactants. Binding to the SLN surface reduced markedly the cytotoxic effect of the surfactants, e.g., up to a factor of 65 for poloxamer 184. The permanent HL60 cell line— differentiated from cells with granulocyte characteristics by retinoic acid treatment—yielded results identical to freshly isolated human granulocytes. In general, the SLNs showed a lower cytotoxicity compared to polyalkylcyanoacrylate and polylactic/glycolic acid (PLA/ GA) nanoparticles.
Conclusions. Because the results are identical when using human granulocytes, differentiated HL60 cells can be used as an easily accessible in vitro test system for i.v. injectable SLN formulations. The SLNs appear suitable as a drug carrier system for potential intravenous use due to their very low cytotoxicityin vitro. 相似文献
88.
Intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity incontinence: do we need urodynamic investigation for outcome assessment?
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