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Janaina Brollo Maximiliano Cassilha Kneubil Edoardo Botteri Nicole Rotmensz Bruno Achutti Duso Luca Fumagalli Marzia Adelia Locatelli Carmen Criscitiello Visnu Lohsiriwat Aron Goldhirsch Maria Cristina Leonardi Roberto Orecchia Giuseppe Curigliano 《Breast (Edinburgh, Scotland)》2013,22(5):856-862
Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes. 相似文献
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S. Saracchini L. Foltran F. Tuccia A. Bassini S. Sulfaro E. Micheli A. Del Conte M. Bertola M. Gion M. Lorenzon S. Tumolo 《Breast (Edinburgh, Scotland)》2013,22(6):1101-1107
Purpose of the studyTrastuzumab combined with sequential chemotherapy with taxanes and anthracyclines as primary systemic therapy achieved high rates of pathologic complete response (pCR). Non-pegylated liposome-encapsulated doxorubicin (NPLD) has shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab with sequential chemotherapy for early or locally advanced HER2 positive BC.MethodsPreoperative treatment included NPLD (60 mg/mq iv) plus cyclophosphamide (600 mg/mq iv) every 3 weeks for 4 cycles followed by docetaxel (35 mg/mq iv) plus trastuzumab (4 mg/mq loading dose iv, then 2 mg/mq iv) weekly for 16 weeks. Primary endpoint was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Clinical staging was exploratory evaluated by CT-PET.Results43 pts were treated from december 2005 to September 2011, 39 of them were evaluable for the purpose of study. Median age was 53 years (range: 31–78), the majority of pts had tumour stage cT2 (63%), tumour grade 3 (86%), clinical nodes involvement N+ (77%), ER positive (56%) and Ki-67 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. There was an association between Ki-67 ≥20% at baseline and pCR (p = 0.018). No cardiac toxicity or discontinuation of trastuzumab was reported. CT-PET modified the clinical stage for 10 patients showing new loco-regional lymph nodes.ConclusionsThis study confirms that integrating anti-HER2 therapy in primary treatment for HER2 positive breast cancer is active. NPLD is a safe option to minimize cardiotoxicity. 相似文献
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BackgroundTrastuzumab is a drug used in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority. The purpose of this study is to evaluate plasma NT-proBNP level and major cardiovascular risk factors as possible early predictors of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.MethodsWe conducted a retrospective observational study involving 66 patients with HER2-positive breast cancer treated with trastuzumab. Left ventricle ejection fraction (LVEF), NT-proBNP values, and the history of cardiovascular risk factors were collected. Cardiotoxicity was diagnosed considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. NT-proBNP cut-off points were considered to establish normal or abnormal values according to patient age.Results27.3% of the patients suffered cardiotoxicity during trastuzumab treatment. Most cases were diagnosed due to the appearance of cardiac symptomatology (66.7%). Logistic regression analysis showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2–28.5, p = 0.028) and high NT-proBNP levels (OR 22.0, 95% CI 5.7–85.4, p < 0.0001) with the development of trastuzumab-induced cardiotoxicity.ConclusionNT-proBNP levels above the upper limit of the normal range adjusted to age or diabetes mellitus seem to be associated with a higher risk of developing cardiotoxicity. However, some limitations of the present study make necessary further studies aimed to clarify whether NT-proBNP and diabetes-associated markers determinations can be useful in the monitoring of cardiotoxicity risk in breast cancer patients undergoing trastuzumab therapy. 相似文献
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BackgroundDual blockade with trastuzumab and pertuzumab combined with neoadjuvant chemotherapy (NACT) has been increasingly used for HER2-positive tumours >2 cm and/or with positive axillary lymph nodes in order to evaluate pathologic response and obtain better surgical management. SB3 is a registered biosimilar trastuzumab approved following a phase III trial demonstrating similar efficacy in the neoadjuvant setting as trastuzumab. However, the study was done without pertuzumab.MethodThe database of the Danish Breast Cancer Group was used to extract data on all patients who started NACT with SB3 and pertuzumab between September 1, 2018 and August 31, 2019. The primary endpoint was pathological complete response (pCR) rate.ResultsIn total 215 patients received NACT and dual blockade. The median age was 55 (24–81). NACT used was cyclophosphamide and epirubicin followed by weekly paclitaxel (62% on six cycles, 35% on eight cycles) or other chemotherapy followed by weekly paclitaxel (3%). Overall, 56% of patients achieved pCR. 60 of 88 node-positive patients pre-NACT achieved ypN0(i-) after neoadjuvant treatment. pCR rate was significantly associated with estrogen receptor status and malignancy grade. An association with CEP17/HER2-ratio was assessed.ConclusionReal world data on dual blockade with SB3 and pertuzumab in combination with NACT in a nationwide population-based study show a pCR rate comparable to that seen in previous clinical studies. 相似文献
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目的 探讨人类表皮生长因子受体-2(HER-2)阳性晚期胃癌中曲妥珠单抗联合IP方案或SOX方案化疗的有效性和安全性。方法 连续性纳入自2015年6月至2017年6月内蒙古医科大学附属医院收治的58例HER-2阳性晚期胃癌,利用随机数字表法分为SOX组和IP组,每组29例。SOX组给予曲妥珠单抗联合替吉奥+奥沙利铂治疗;IP组给予曲妥珠单抗联合伊立替康+顺铂治疗,比较两个疗程后两组病人血清肿瘤标志物和新生血管标志物的变化,以及化疗效果和不良反应差异。结果 两个治疗疗程后,两组病人血清肿瘤标志物癌胚抗原(CEA),糖类蛋白19-9(CA19-9),糖类抗原125(CA125)以及组织多肽特异性抗原(TPS)水平均差异无统计学意义(t=0.628,P=0.532;t=0.879,P=0.383;t=0.828,P=0.411;t=0.719,P=0.476);新生血管标志物内皮生长因子(VEGF)、血管生成素-2(Ang-2)、内皮抑素(ES)、色素上皮衍生因子(PEDF)水平亦差异无统计学意义(t=0.701,P=0.486;t=0.955,P=0.343;t=1.803,P=0.077;t=0.991,P=0.326;);SOX组客观有效率(ORR)及病控制率(DCR)分别为44.83%和82.76%;IP组ORR及DCR分别为34.48%和69.97%,均差异无统计学意义(χ2=0.648,P=0.421;χ2=1.506,P=0.219)。但IP组骨髓抑制(58.62%)和恶心呕吐(3.45%)发生率明显高于SOX组(31.03%,6.90%),差异有统计学意义(χ2=4.461,P=0.035;χ2=5.836,P=0.016)。结论 曲妥珠单抗联合SOX化疗方案或IP方案在HER-2阳性晚期胃癌病人中疗效相当,但SOX方案不良反应发生率较少,值得临床推广。 相似文献
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《Breast (Edinburgh, Scotland)》2014,23(5):637-643
BackgroundRecently, HER3-expression was postulated as independent risk factor for metastatic spread. Therefore, we investigated the role of HER3 expression as prognostic marker in metastatic breast cancer patients.MethodsPatients of different breast cancer subtypes diagnosed with metastatic disease (visceral and/or brain metastases) were identified from a breast cancer database. Tissue samples of the respective primary tumors were retrieved, and immunohistochemical staining for estrogen-receptor, progesterone-receptor, HER2, and HER3 was performed. In HER2 equivocal and selected HER3 positive cases, subsequent fluorescent in situ hybridization (FISH) analysis was performed.ResultsTissue specimens of 110 patients were available for this analysis. 21% had strong, complete, membranous HER3 staining of at least 10% of all tumor cells; HER3 protein expression was not associated with HER3 gene amplification. HER2/HER3 co-overexpression was observed in 12/110 (11%) specimens and HER3-overexpression showed a statistically significant association with HER2-overexpression (p = 0.02). No correlation was observed for HER3-overexpression and overall survival (OS), time to diagnosis of brain metastases, and incidence of brain metastases. Still, in patients with HER3 overexpression, a higher rate of ‘brain only’ metastatic behavior was observed (p = 0.042). In the HER2-positive subgroup, HER3-overexpression was significantly associated with shorter OS from diagnosis of metastatic disease (median 17 vs. 35 months; p = 0.04; log rank test).ConclusionsHER2/HER3 co-overexpression is significantly associated with impaired OS from diagnosis of metastatic disease in patients with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or the inhibition of HER2/HER3 hetero-dimerization may improve clinical outcome in this subgroup. 相似文献
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