首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1073篇
  免费   62篇
  国内免费   2篇
耳鼻咽喉   28篇
儿科学   18篇
妇产科学   7篇
基础医学   142篇
口腔科学   16篇
临床医学   112篇
内科学   228篇
皮肤病学   8篇
神经病学   98篇
特种医学   55篇
外科学   179篇
综合类   4篇
一般理论   2篇
预防医学   85篇
眼科学   8篇
药学   60篇
中国医学   6篇
肿瘤学   81篇
  2024年   2篇
  2023年   9篇
  2022年   5篇
  2021年   32篇
  2020年   8篇
  2019年   25篇
  2018年   69篇
  2017年   29篇
  2016年   34篇
  2015年   42篇
  2014年   45篇
  2013年   54篇
  2012年   112篇
  2011年   79篇
  2010年   50篇
  2009年   29篇
  2008年   92篇
  2007年   71篇
  2006年   67篇
  2005年   74篇
  2004年   55篇
  2003年   47篇
  2002年   51篇
  2001年   13篇
  2000年   16篇
  1999年   3篇
  1995年   2篇
  1992年   5篇
  1991年   3篇
  1990年   2篇
  1989年   3篇
  1988年   1篇
  1987年   1篇
  1986年   2篇
  1985年   2篇
  1983年   1篇
  1971年   2篇
排序方式: 共有1137条查询结果,搜索用时 15 毫秒
81.
PurposeThe European medicines agency (EMEA) has stated that the degree of pre-treatment could modify the patient’s tolerance to new treatments in paediatric oncology. It is current practice to divide a phase I trial into two groups to identify the maximum tolerated dose (MTD) in each group separately. The aim of this study was to investigate the relevance of this approach.MethodsWe reanalysed a large phase I trial of Irinotecan that included 80 children (32 heavily pretreated patients and 48 less heavily pretreated). An extended simulation study was performed to investigate the robustness of the conclusions in the context of small sample sizes. Dose recommendations were studied according to scenarios with group differences, as measured by odds ratio (OR), ranging from 1 (no difference) to 10 (large difference) and sample sizes increasing from 20 × 2 to 60 × 2 patients.ResultsThis study shows a high risk of misidentification of the MTD in each of the two groups, regardless of the group difference. With a group difference corresponding to OR = 8 and balanced sample sizes (20 × 2 patients), the same MTD was identified in 11% of the simulations. Even with larger sample sizes (40 × 2 patients), this figure reached 24% for OR = 3. There is also a very high risk of identifying two different MTD (52% for 40 × 2 patients) although the risk is similar in both groups.ConclusionsTwo independent sample designs in paediatric phase I trials should be avoided or reserved to limited situations when there is a strong rationale possibly based on adult data.  相似文献   
82.
83.
Purpose  Many surgical techniques have been published on how to treat congenital pseudoarthrosis of the tibia (CPT). We combined Ilizarov’s fixator with intramedullary nailing of the tibia and developed a procedure which combines the advantages of both methods: Ilizarov’s high fusion rate with alignment control and the protection against refracture provided by the intramedullary nail. The results of this approach are presented and discussed. Material and methods  Seven boys and three girls aged 3–14 years (mean age 8 years 2 months) were treated using our combined technique. In six cases, the CPT was associated with neurofibromatosis. Two strategies were adopted: in six cases, a compression was applied on the bone defect, and in four cases, segmental bone transportation was performed before the compression procedure. The final follow-up (1.2–6.6 years) included a clinical and radiological examination. Results  Tibial union was achieved in nine cases without bone grafting. In one case, tibial union still remains uncertain, despite intertibiofibular bone grafting and additional compression procedures. Thirteen overall complications were noted, including three valgus deformity of the ankle. Bone transportation failed to achieve complete limb lengthening in three cases. One deep infection occurred 4 years after removal of the external fixator. The treatment for this included nail removal and antibiotic therapy for 3 months. Despite a permanent protection of orthosis, a refracture occurred 2 years after nail removal, reverting to the initial level of pseudarthrosis. Another surgical attempt using the same method was then performed with a satisfactory result. Conclusions  The association of Ilizarov’s technique and intramedullary nailing achieved and maintained tibial union in nine of ten patients at final follow-up. It also allowed correction of axial deformities and prevented refracture. Despite the short duration of the follow-up and a high rate of complications in our series, this method can be useful in many cases of CPT in which healing has failed to occur despite many previous surgeries.  相似文献   
84.
We assessed the subjective quality of life (QOL) of 30 deficit schizophrenic patients compared to 112 nondeficit schizophrenic patients. The deficit patients did not differ in term of QOL, total score of positive symptoms, general psychopathology from the nondeficit patients. This result suggested an absence of impact of primary negative symptoms on the subjective QOL in schizophrenic patients.  相似文献   
85.
BACKGROUND: Dialysis is becoming increasingly frequent in patients over 75 years of age. Age is a superimposed comorbid factor commonly associated with poor prognosis in these patients. OBJECTIVE: To analyze the survival of 292 patients aged over 75 years on initiation of peritoneal dialysis (PD) from September 1982 to September 1999. DESIGN: Retrospective study. SETTING: Nephrology department in a University Hospital. RESULTS: Mean age was 81.5 years (range 75-92 years); 178 patients were over 80 years and 60 patients were over 85 years. Sex ratio was 136F/156M. Ninety-day mortality rate was 12%. Excluding the first 3 months, median patient survival was 21.6 months; 226 patients died on PD and 24 were shifted to hemodialysis. Survival was inversely correlated with the Charlson combined comorbidity index (CCI), but independent of predialysis hemoglobin and serum albumin levels. Over three selected periods, 1982-1989, 1989-1995, and 1995-1999, an increase was found in mean age (79.7 +/- 3.3, 82.6 +/- 3.9, and 81.8 +/- 4.4 years; p < 0.001), CCI (7.6 +/- 1.59, 8.0 +/- 1.52, and 8.5 +/- 1.63; p = 0.01), and predialysis creatinine clearance (6.2 +/- 2.3, 6.4 +/- 2.4, and 9.8 +/- 3.8 mL/minute; p < 0.001). Median survival was similar in the various selected periods (21.0, 21.5, and 25.4 months). The incidence of peritonitis decreased from 0.63 to 0.21 episodes per patient year. CONCLUSION: From 1982 to 1999, mean age and comorbidity increased on initiation of dialysis in elderly patients, with no increase in mortality. Survival in elderly patients on PD was related to the age-comorbidity index.  相似文献   
86.
We combined tissue culture and flow cytometry to assess the activities of various temperatures, chemicals, and disinfectants on the viability and infectivity of spores of Encephalitozoon intestinalis. Surfanios and benzalkonium chloride, disinfectants currently used in the hospital, were remarkably efficient in destroying spore viability and infectivity.  相似文献   
87.

Purpose

Stress cardiomyopathy is a common life-threatening complication after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that left ventricular (LV) longitudinal strain alterations assessed with speckle tracking could identify early systolic function impairment.

Methods

This was an observational single-center prospective pilot controlled study conducted in a neuro-intensive care unit. Forty-six patients with severe SAH with a World Federation of Neurological Surgeons grade (WFNS) ≥III were included. Transthoracic echocardiography (TTE) was performed on day 1, day 3, and day 7 after the patient’s admission. A cardiologist blinded to the patient’s management analyzed the LV global longitudinal strain (GLS). The control group comprised normal subjects matched according to gender and age.

Results

On day 1 median (25th–75th percentile) GLS was clearly impaired in SAH patients compared to controls [?16.7 (?18.7/?13.7) % versus ?20 (?22/?19) %, p < 0.0001], whereas LVEF was preserved [65 (59?70) %]. GLS was severely impaired in patients with a WFNS score of V versus III–IV [?15.6 (?16.9/?12.3) % versus ?17.8 (?20.6/?15.8) %, p = 0.008]. Seventeen (37 %) patients had a severe GLS alteration (>?16 %). In these patients, GLS improved from day 1 [?12.4 (?14.8/?10.9) %] to last evaluation [?16.2 (?19/?14.6) %, p = 0.0007] in agreement with the natural evolution of stress cardiomyopathy.

Conclusions

On the basis of LV GLS assessment, we demonstrated for the first time that myocardial alteration compatible with a stress cardiomyopathy is detectable in up to 37 % of patients with severe SAH while LVEF is preserved. GLS could be used for sensitive detection of stress cardiomyopathy. This is critical because cardiac impairment remains a major cause of morbidity and mortality after SAH.
  相似文献   
88.
89.
Overcoming multidrug resistance in taxane chemotherapy.   总被引:3,自引:0,他引:3  
Paclitaxel (Taxol) and docetaxel (Taxotère) are currently two of the most important anticancer drugs in cancer chemotherapy. However, clinical treatment with these taxane agents often encounters undesirable side effects and multidrug resistance (MDR) caused by overexpression of P-glycoprotein (Pgp). Photoaffinity labeling of Pgp using photoreactive radiolabeled paclitaxel analogs along with molecular modeling has revealed a unique binding region for paclitaxel on the C-terminal half of Pgp. Highly efficient taxane-based MDR reversal agents (TRAs) have been developed. Extensive structure-activity relationship (SAR) studies have led to the development of new generation taxanes that possess 2-3 orders of magnitude higher potencies against human cancer cell lines expressing the MDR phenotype. One of these taxanes, SB-T-1 10131 (IDN5109, BAY59-8862), exhibits excellent activity against a variety of drug-sensitive and drug-resistant cancer cell lines as well as human tumor xenografts in mice. This taxane is orally active with excellent bioavailability, and is currently undergoing phase II human clinical trials. Novel taxane-antibody immunoconjugates have shown very promising results for tumor-specific delivery and release of an extremely cytotoxic taxane, wherein epidermal growth factor receptor is used as the specific antigen on the tumor surface of human squamous cancer xenograft in SCID mice.  相似文献   
90.
OBJECTIVE: Although mechanical ventilation is required in 30% of patients with Guillain-Barré syndrome, early predictors of this treatment remain unknown. DESIGN: Analysis of two cohorts of patients enrolled in two multicenter randomized clinical trials. SETTING: French intensive care and neurologic units. MEASUREMENTS: Demographic, neurologic, and biologic data; vital capacity; and time of onset, admission, and endotracheal mechanical ventilation were collected. RESULTS: Amid 722 consecutive adults not ventilated at admission, endotracheal mechanical ventilation was required in 313 (43%) patients. Multivariate analyses identified six predictors of endotracheal mechanical ventilation: time from onset to admission of <7 days (odds ratio, 2.51), inability to cough (odds ratio, 9.09), inability to stand (odds ratio, 2.53), inability to lift the elbows (odds ratio, 2.99) or head (odds ratio, 4.34), and liver enzyme increases (odds ratio, 2.09). In the 196 (27%) patients whose vital capacity was measured, time from onset to admission of <7 days (odds ratio, 5.00), inability to lift the head (odds ratio, 5.00), and vital capacity <60% (odds ratio, 2.86) predicted endotracheal mechanical ventilation. CONCLUSIONS: Patients with at least one of these predictors should be monitored in an intensive care unit. Mechanical ventilation was required in >85% of patients with at least four predictors from the first multivariate model and in 85% of patients with all three predictors from the second multivariate model. In these patients at high risk of respiratory failure, the value of early mechanical ventilation may deserve investigation.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号