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The seventh leading cause of cancer-related death globally, pancreatic ductal adenocarcinoma (PDAC) involves the exocrine pancreas and constitutes greater than 90% of all pancreatic cancers. Surgical resection in combination with systemic chemotherapy with or without radiation remains the mainstay of treatment and the only potentially curative treatment option. While there has been improvement in systemic chemotherapy, long-term survival among patients with PDAC remains poor. Improvement in the understanding of tumorigenesis, genetic mutations, the tumor microenvironment (TME), immunotherapies, as well as targeted therapies continued to drive advances in PDAC treatment. We herein review the TME, genetic landscape, as well as various metabolic pathways associated with PDAC tumorigenesis relative to emerging therapies. 相似文献
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《Journal of infection and chemotherapy》2022,28(2):352-355
IntroductionMonoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021.MethodsAccording to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan.ResultsDuring Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12–0.53) and 0.10 (95% CI: 0.01–0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event.ConclusionsThe administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse. 相似文献
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Maja Popovic Gorana Matovina-Brko Masa Jovic Lazar S Popovic 《World journal of clinical oncology》2022,13(1):28-38
Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with inter mediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozan tinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment. 相似文献
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《Advances in medical sciences》2022,67(2):364-378
PurposeAlthough skin cutaneous melanoma (SKCM) is a relatively immunotherapy-sensitive tumor type, there is still a certain fraction that benefits less from treatment. Ferroptosis has been demonstrated to modulate tumor progression in many cancer types. This study focused on ferroptosis-related genes to construct a prognostic model for SKCM patients.Materials and methodsGene expression profiles of SKCM samples were obtained from public databases. Unsupervised consensus clustering was used to determine molecular subtypes related to ferroptosis. Least absolute shrinkage and selection operator (LASSO) and stepwise Akaike information criterion (stepAIC) were applied to construct a prognostic model based on differentially expressed genes between two molecular subtypes.ResultsC1 and C2 subtypes were identified with differential prognosis and immune infiltration. A 7-gene prognostic model was constructed to classify samples into high-FPRS and low-FPRS groups. Low-FPRS group with favorable prognosis had higher immune infiltration and more enriched immune-related pathways than the high-FPRS group. The two groups showed distinct sensitivity to immunotherapy, with the low-FPRS group predicted to have more positive response to immunotherapy than the high-FPRS group. A nomogram based on the FPRS score and clinical features was built for more convenient use.ConclusionsThe critical role of ferroptosis involved in SKCM development was further validated in this study. The prognostic model was efficient and stable to be applied in clinical conditions to support clinicians in determining personalized therapy for SKCM patients especially those with metastasis. 相似文献
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宫颈癌严重威胁全球女性的生命健康,晚期宫颈癌治疗手段有限,5年生存率不到20%,是妇科肿瘤的巨大挑战。免疫治疗是晚期宫颈癌患者的重要治疗手段之一,包括免疫检查点抑制剂、治疗性疫苗和过继性T细胞免疫疗法等,但免疫治疗耐药性使部分患者无应答而效果不佳。因此,迫切需要深入研究和探讨免疫耐药的机制从而改善耐药,现归纳总结了近年有关宫颈癌中免疫耐药机制的相关研究,主要分为肿瘤内在因素和外在免疫环境改变等因素,并介绍针对免疫耐药提出的应对措施及进展。 相似文献
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《Bulletin du cancer》2022,109(10):1066-1072
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Hyperprogressive disease (HPD) is a concerning paradoxical acceleration of cancer growth induced by immune drugs. The lack of standard radiological criteria makes its study challenging. We reviewed the literature and compared the main criteria for HPD proposed by Ferté, Le Tourneau, Garralda and Caramella to address this relevant unmet need in Immune-oncology.Among 182 consecutive patients with advanced cancer treated with immunotherapy in early-phase clinical trials, 71 with progressive disease at the first evaluation were eligible. HPD patients were studied regarding tumor growth dynamics and clinical impact.HPD occurred in 17 (23.9%), 17 (23.9%), 23 (32.4%) and 6 (8.4%) patients, as defined by Ferté, Le Tourneau, Garralda and Caramella, respectively. The strongest association was found between the Ferté and Le Tourneau criteria (Kappa = 0.61), and the Jaccard similarity index varied from 55% (Ferté and Le Tourneau) to 21% (Le Tourneau and Caramella). The Ferté and Le Tourneau criteria showed statistically significant differences between pre-baseline and post-baseline tumor growth rate in patients with HPD, which could not be confirmed with the Caramella and Garralda criteria. Significant differences in progression-free survival were observed between non-hyperprogressors and hyperprogressors, with all criteria. The proportion of patients that could not receive additional lines of therapy was higher in the HPD group.HPD is an immunotherapy-related acceleration of tumor growth kinetics, with a consequent negative clinical impact. Pre-baseline CT scans and tumor growth rate evaluations are required to identify HPD. Our analysis favors the use of the Le Tourneau method, as it captures adequately the HPD phenomenon and is more convenient to use. 相似文献