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1.
Jinhui Ma Kerry Siminoski Peiyao Wang Jacob L Jaremko Khaldoun Koujok Mary Ann Matzinger Nazih Shenouda Brian Lentle Nathalie Alos Elizabeth A Cummings Josephine Ho Kristin Houghton Paivi M Miettunen Rosie Scuccimarri Frank Rauch Leanne M Ward the Canadian STOPP Consortium 《Journal of bone and mineral research》2021,36(7):1255-1268
Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study, we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over 2 years in glucocorticoid-treated children (n = 343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score <−1.4), and the non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy X-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semiquantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% confidence interval [CI] 8–15) with 46% of IVF (95% CI 30–61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI 57–85) but would require radiographs in 37% of children (95% CI 32–42). In the non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI 83–91), the greatest overall accuracy at 82% (95% CI 78–86), and the lowest radiography rate at 17% (95% CI 14–22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI 67–92), but required radiographs in 65% (95% CI 60–70). These results provide guidance for targeting spine radiography in children at risk for IVF. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
2.
Shenouda G Labateya M Souhami L Donath D Vuong T Joseph L 《International journal of oncology》1993,2(1):115-118
Tumour necrosis factor (TNF) has been implicated in the pathogenesis of cachexia in neoplastic and infectious diseases. In our study, the relationship between TNF and other cytokines in patients with malignancy was studied by measuring the serum levels of TNF, Interleukin-I (IL-1), Interleukin-2 (IL-2), and Interleukin-6 (IL-6). Eight patients with cancer had weight loss >10% of their body weight prior to starting anticancer therapy, and their weight loss was not attributable to gastrointestinal disorder, or other medical conditions. Seven patients with malignancy and no weight loss, as well as three normal donors without malignancy were also tested as controls. TNF, IL-1, IL-2 and IL-6 serum levels were determined using a quantitative ELISA test. Elevated levels of TNF, IL-1, IL-2 and IL-6 were detected in 25%, 12.5%, 12.5% and 50% of patients, respectively. In contrast, TNF levels were elevated in 28.5% of seven patients with cancer and no weight loss. In these patients, IL-1, IL-2 and IL-6 levels were undetectable. No TNF, IL-1, IL-2 or IL-6 could be detected in the sera of normal controls. Elevated cytokines serum levels, and especially IL-6, are detected in patients with cancer-cachexia. The determination of such cytokines may have a prognostic value. 相似文献
3.
Muanza T Shenouda G Souhami L Leblanc R Mohr G Corns R Langleben A 《The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques》2000,27(4):302-306
PURPOSE: To assess the feasibility and the toxicity of adjuvant high dose tamoxifen (TAM) and postoperative brain irradiation for patients with newly-diagnosed glioblastoma multiforme (GBM). MATERIAL AND METHODS: Twelve patients with histopathologically confirmed GBM entered the study. There were nine males and three females, with median age of 48.8 years (range 30-75 years). Karnofsky performance status (KPS) was 60-70% for four patients and 80-100% for eight patients. Based on the Radiation Therapy Oncology Group recursive partition analysis, there were three class III patients, six class IV, one class V, and two class VI. Eleven patients underwent partial surgical tumor resection and one patient had a near complete resection. Two weeks post surgery, the patients were started on high dose TAM (120 mg/m2 P.O. BID for three months). Two weeks from date of starting TAM, external beam radiotherapy (RT) was given at a dose of 59.4 Gy/33 qd fractions/6.5 weeks. Patients were assessed weekly for toxicity during treatment. Imaging studies were done at the end of two weeks of TAM, then monthly. RESULTS: Median follow-up was 40 weeks (range 22-84 weeks). In one patient, TAM was associated with significant vomiting, necessitating the TAM dose to be decreased at three weeks and then stopped at two months. One other patient had bilateral deep venous thrombosis after 52 weeks on TAM, although the relationship to TAM was not firmly established. There were no radiological responses after two weeks of TAM or at the end of RT. The median time to progression was 17.7 weeks (range 5.1-43.8 weeks). Median survival time was 33.4 weeks (range 10-79.7). Actuarial survival at 48 and 74 weeks was 40% and 15%, respectively. CONCLUSION: Our study shows that adjuvant high dose TAM is feasible and relatively well-tolerated. Furthermore, the combined use of high dose TAM and RT postoperatively was not associated with any significant increase in radiation-induced neurological toxicity. However, high dose TAM does not appear to improve treatment results. 相似文献
4.
Slusarz A Jackson GA Day JK Shenouda NS Bogener JL Browning JD Fritsche KL Macdonald RS Besch-Williford CL Lubahn DB 《Endocrinology》2012,153(9):4160-4170
Previous evidence suggests soy genistein may be protective against prostate cancer, but whether this protection involves an estrogen receptor (ER)-dependent mechanism is unknown. To test the hypothesis that phytoestrogens may act through ERα or ERβ to play a protective role against prostate cancer, we bred transgenic mice lacking functional ERα or ERβ with transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Dietary genistein reduced the incidence of cancer in ER wild-type (WT)/transgenic adenocarcinoma of mouse prostate mice but not in ERα knockout (KO) or ERβKO mice. Cancer incidence was 70% in ERWT mice fed the control diet compared with 47% in ERWT mice fed low-dose genistein (300 mg/kg) and 32% on the high-dose genistein (750 mg/kg). Surprisingly, genistein only affected the well differentiated carcinoma (WDC) incidence but had no effect on poorly differentiated carcinoma (PDC). No dietary effects have been observed in either of the ERKO animals. We observed a very strong genotypic influence on PDC incidence, a protective effect in ERαKO (only 5% developed PDC), compared with 19% in the ERWT, and an increase in the incidence of PDC in ERβKO mice to 41%. Interestingly, immunohistochemical analysis showed ERα expression changing from nonnuclear in WDC to nuclear in PDC, with little change in ERβ location or expression. In conclusion, genistein is able to inhibit WDC in the presence of both ERs, but the effect of estrogen signaling on PDC is dominant over any dietary treatment, suggesting that improved differential targeting of ERα vs. ERβ would result in prevention of advanced prostate cancer. 相似文献
5.
6.
Nazih H Raffi F Taïeb A Reynes J Choutet P Cassuto JP Ferry T Chêne G Leport C Bard JM;Aproco-Copilote Anrs Co Study Group 《AIDS research and human retroviruses》2012,28(4):393-399
Highly active antiretroviral therapy (HAART) is associated with fat redistribution and metabolic disorders. The present study was undertaken to evaluate the association between peroxisome proliferator activated receptor (PPAR)α and PPARγ polymorphisms, two genes involved in lipid metabolism and adipocyte differentiation, and elements of the metabolic syndrome, lipodystrophy, or carbohydrate metabolism abnormalities in patients receiving HAART. The frequency distribution of rare alleles for PPARα (L162V) and PPARγ (P12A and H449H) was compared using the chi square test in 363 HIV-1-infected patients classified according to the presence or absence of the metabolic syndrome after 48 months of follow-up on their first PI-containing regimen. The P12A rare g allele was present in 12% patients with normal glucose metabolism, 11% patients with impaired glucose tolerance or impaired fasting glucose, and 35% patients with diabetes (p=0.014). The rare g allele for L162V was present in 14% of patients free of hypertriglyceridemia and in 7% patients with hypertriglyceridemia (p=0.04). The rare g allele for L162V was found in 15% of patients free of any sign of lipodystrophy and 8% with at least one sign of lipodystrophy (p=0.04) and the rare t allele for H449H was found in 14% of patients free of any sign of lipodystrophy and 23% of patients with at least one sign of lipodystrophy (p=0.05). There was no convincing association between any polymorphism of PPARα and PPARγ and each individual component of the metabolic syndrome, except for the relationship of the P12A polymorphism with diabetes. Confirmatory studies on a larger number of individuals are needed. 相似文献
7.
8.
David J. Peterson MD Pauline T. Truong MDCM Betro T. Sadek MD Cheryl S. Alexander CHIM Bradley Wiksyk BSc Mina Shenouda MD Rita Abi Raad MD Alphonse G. Taghian MD PhD 《Annals of surgical oncology》2014,21(11):3490-3496
Background
While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy.Methods
Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group.Results
Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p < 0.001) and trastuzumab therapy (50 vs 57 %, p = 0.04). The 5-year outcomes in women treated with BCT compared with mastectomy were: LRRFS 98.0 versus 98.3 % (p = 0.88), BCSS 97.2 versus 96.1 % (p = 0.70), and OS 95.5 versus 93.4 % (p = 0.19). Trastuzumab was associated with similar LRRFS and improved OS in both local treatment groups.Conclusions
BCT is safe in the population of women with pT1–2, N0, HER2+ breast cancer, providing high rates of locoregional control and survival equivalent to mastectomy. Trastuzumab was associated with improved survival in both groups. 相似文献9.
V. Phan T. Blydt-Hansen J. Feber N. Alos S. Arora S. Atkinson L. Bell C. Clarson R. Couch E. A. Cummings G. Filler R. M. Grant J. Grimmer D. Hebert B. Lentle J. Ma M. Matzinger J. Midgley M. Pinsk C. Rodd N. Shenouda R. Stein D. Stephure S. Taback K. Williams F. Rauch K. Siminoski L. M. Ward 《Osteoporosis international》2014,25(2):627-637
Summary
Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.Introduction
Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.Methods
VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.Results
Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3–17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2–15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), ?0.5?±?1.1; p?=?0.001) and at 3 months (?0.6?±?1.1; p?<?0.001), but not at 6 months (?0.3?±?1.3; p?=?0.066) or 12 months (?0.3?±?1.2; p?=?0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p?=?0.003). A subgroup (N?=?16; 25 %) had LS BMD Z-scores that were ≤?1.0 at 12 months. In these children, each additional 1,000 mg/m2 of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, ?0.71 to ?0.07; p?=?0.017).Conclusions
The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤?1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort. 相似文献10.
Kerry Siminoski Brian Lentle Mary Ann Matzinger Nazih Shenouda Leanne M. Ward 《Pediatric radiology》2014,44(4):457-466