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1.
Purpose: To investigate the possible relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin (OPN) levels measured in mouse serum.

Material and methods: Experiments were performed in CDF1 mice that were either non-tumour bearing or with different sized tumours implanted in the right rear foot. Osteopontin levels in extracted mouse blood serum and tissue from the transplanted tumours were measured using an ELISA assay. The tumour oxygenation status was estimated using the Eppendorf Histograph and the fraction of oxygen partial pressure (pO2) values ≤5 mm Hg (HF5) was calculated. Necrosis was measured in haematoxylin and eosin-stained sections. Tumour hypoxia was increased by placing animals in a low-oxygen (10%) environment. Single radiation doses (240 kV x-rays) were given locally to tumours under ambient or clamped conditions and response assessed using a tumour control assay.

Results: Serum OPN levels increased linearly with increasing tumour volume and this increase correlated with tumour OPN. HF5 and necrosis also increased with increasing tumour volume, but this increase was non-linear. Converting the HF5 results into equivalent tumour volume gave results that were directly correlated to OPN serum levels. Placing mice in a 10% oxygen environment for 12 hours significantly increased HF5. However, serum OPN only increased if reoxygenation occurred before measurement. Radiobiological hypoxic fraction in this tumour model did not change with increasing tumour size, but the total number of hypoxic cells did increase.

Conclusions: These findings suggest that serum OPN measurement may predict the proportion of hypoxic cells in this tumour model, although increased serum OPN levels simply resulting from an increased tumour burden can not be ruled out.  相似文献   
2.
近年来,骨代谢标志物临床应用已取得了显著的进展,这些指标的测量,让我们对骨质疏松症的发病机制有一个更好的了解。骨代谢标志物用于选择骨质疏松治疗药物和评价药物疗效。因此,合理应用和评价骨代谢标志物在临床实践中是非常重要的。为了实现这些目标,由日本骨质疏松症学会授权的骨质疏松骨代谢指标应用指南制定委员会,总结骨代谢指标最新研究进展,并提出了骨代谢指标的合理应用。虽然现在骨代谢指标,在骨质疏松症的日常管理工作中具有重要的作用,但由于医保范围的限制,在日本的应用仍不普遍。自日本骨质疏松症学会制定了2001年指南,新的骨代谢指标已列入临床实践。新的促进骨形成的骨质疏松症治疗方法,改变了骨代谢指标在临床实践中的应用。因此,需要调整目前的临床应用方案,提出制定新的2012年指南的建议。  相似文献   
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目的采用不同频率的脉冲电磁场干预骨保护素基因敲除小鼠骨质疏松模型,探讨脉冲电磁 场治疗骨质疏松的最适治疗频率。方法8周龄雌雄各半骨保护素基因敲除小鼠30只,随机分为 A、B、C 3组,每组10只,粤组为空白对照组,不进行干预;B组小鼠每天在强度为4皂栽,频率为8 HZ 的磁场中照射治疗20 min,共30 d;C组小鼠每天在强度为4 mT,频率为32 HZ的磁场中照射治疗20 min,共30凿。各组小鼠在治疗前及治疗30d后用酶联免疫法(ELISA )法检测抗酒石酸酸性磷酸酶 缘遭及血清骨钙素值。结果8HZ、32HZ两治疗组在治疗后抗酒石酸酸性磷酸酶5遭,血清骨钙素含 量与A对照组之间比较差异有统计学意义(P <0.05 ), 8 HZ、32 HZ两治疗组之间治疗前与治疗后所 测三种指标比较差异无统计学意义(P >0.05 )。结论脉冲电磁场对骨保护素基因敲除小鼠骨质疏 松有肯定治疗效果,应用频率为8-32 HZ的磁场治疗能产生相同的治疗效果。  相似文献   
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背景与目的 结直肠癌(CRC)是全球第三大最常诊断的恶性肿瘤和第二大癌症死亡原因。最新指南推荐所有的CRC患者需要进行微卫星不稳定(MSI)的检测。MSI患者往往具有错配修复蛋白缺失(dMMR)。MSI/dMMR状态已被用作生物标志物预测对免疫治疗的有利反应和预后。然而MSI特征基因及其与肿瘤浸润的免疫细胞的关系未进行阐述。因此本研究通过使用机器学习的方式发掘CRC中新型的MSI特征基因,并且验证其的诊断价值及其与免疫细胞浸润的关系。方法 按照纳入排除标准,将GEO数据库中GSE39582数据集作为训练集,将TCGA数据库中COAD数据集作为外部验证集。使用机器学习的方法(LASSO回归、SVM-RFE算法),在GSE39582结直肠癌数据集中筛选MSI特征基因,并在TCGA结直肠癌数据中进行验证。采用受试者工作特征(ROC)曲线和曲线下面积(AUC)评价基因对MSI的诊断效能。CIBERSORT算法评估肿瘤样本浸润的免疫细胞成分,Spearman相关性分析验证MSI特征基因和免疫细胞的关系。结果 训练集共纳入536例CRC患者,其中高频MSI(MSI-H)77例(14.37%)。在验证集中,共计389例CRC患者,其中MSI-H 67例(17.22%)。基线资料分析显示,MSI-H/dMMR CRC的TNM分期存活率优于低频MSI(MSI-L)或微卫星稳定(MSS)/错配蛋白完整(pMMR)CRC(P<0.05)。在GSE39582数据集中,LASSO回归筛选MSI特征基因21个,SVM-RFE算法筛选基因6个,结合两种算法确定MSI特征基因为EIF5ACXCL13HNRNPLHOXC6RPL22L1Y16709。在TCGA数据库中进一步验证MSI特征基因的诊断效能,研究发现EIF5A的诊断效能最高。在训练集和验证集中,EIF5A的AUC值分别为0.922和0.805。同时,Spearman相关性分析发现,EIF5A主要与CD8+T细胞,活化的树突状细胞,辅助性T细胞,M1型巨噬细胞,γδT细胞,中性粒细胞成正相关;与CD4+记忆性T细胞,M2型巨噬细胞,静止树突状细胞,嗜酸性粒细胞,调节性T细胞呈负相关。结论 CRC的新型MSI特征基因分析结果表明,EIF5A对CRC MSI的诊断具有较好的诊断作用和临床价值,同时提示EIF5A与免疫细胞及免疫微环境相关。因此,EIF5A可能成为免疫检查点治疗的新型标志物。  相似文献   
7.
J Oral Pathol Med (2010) 39 : 223–229 Background: The aim of this study was to assess the expression, distribution and comparison of tenascin, a glycoprotein of the extracellular matrix in ameloblastoma and ameloblastic fibroma, both odontogenic neoplasms with diverse biological behavior and to understand the proliferative activity by using the morphometric analysis. Methods: Paraffin embedded tissue from 25 cases of odontogenic tumors i.e., ameloblastoma (n = 15) and ameloblastic fibroma (n = 10) were used. The expression of tenascin was evaluated using immunohistochemistry. Morphometric analysis of nucleolar organizer regions (NORs) from ameloblastoma and ameloblastic fibroma was carried out by silver staining. Results: A heterogeneous expression of tenascin was found in ameloblastoma which was mainly localized at the epithelial–mesenchymal interface and a patchy distribution was observed in the stroma (80%), while strong positivity was observed in the stroma and at the basement membrane zone of ameloblastic fibroma (100%). argyrophilic nucleolar organizer regions (AgNORs) revealed higher mean counts in ameloblastoma (3.093 ± 0.902) when compared with those of ameloblastic fibroma (1.553 ± 0.250). Ameloblastoma presented more than two NORs (two to five) per nucleus in majority of the cells, while ameloblastic fibroma exhibited only one NORs per nucleus. Conclusions: Expression of tenascin in these neoplasms suggest that it could play a role in epithelial‐ mesenchymal interaction, while AgNORs reveal that ameloblastomas are more aggressive when compared with ameloblastic fibromas.  相似文献   
8.
A phase III trial of S‐1 plus cisplatin (SP) versus S‐1 alone, for first‐line treatment of advanced gastric cancer (SPIRITS trial), has shown that overall survival was better in patients treated with SP than with S‐1 alone. In the present retrospective biomarker study, we aimed to develop a methodology to identify the patients with advanced gastric cancer who would respond better to S‐1 alone than SP. We studied 120 patients who received S‐1 alone or SP for first‐line chemotherapy for advanced gastric cancer, and quantitatively evaluated mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase, vascular endothelial growth factor‐A, and epidermal growth factor receptor in paraffin‐embedded specimens of primary tumors. Multivariate survival analysis in patients who received S‐1 monotherapy (66 patients) demonstrated that low TP expression (hazard ratio: 2.55 (95% CI: (1.33 to 4.89)), low TS (2.71 (1.36 to 5.37)), and high OPRT (0.33 (0.13 to 0.86)) were significant predictors of long overall survival. In patients with lower expression of both TP and TS (n = 23) than their cutoff values, the S‐1 alone group (n = 15) had longer overall survival than the SP group (n = 8; median overall survival, 18.2 months vs. 9.4 months), whereas the frequency of overall adverse events in the S‐1 alone group tended to be lower than that in SP group. Our results suggest that these biomarkers are useful for selection of patients with advanced gastric cancer in whom treatment with S‐1 alone will yield survival benefit.  相似文献   
9.
Depression is considered as a chronic and recurring illness with functional impairment, significant disability, morbidity and mortality. Despite the extensive research carried out on depression, its pathophysiology is still poorly understood. An important problem concerning research into depressive disorder is the lack of biological markers which could improve diagnosis or indicate a risk of developing depression or risk of relapse. Several reports indicated decreased zinc concentrations and even its deficit in clinical depression, so the measurement of the concentration of this element in the blood of patients was suggested as a useful and specific clinical marker of depression. The reported results indicated that the serum zinc level might be a marker of depression as a state (state marker) in treatment responsive patients. However, in drug-resistant depression a decreased concentration of zinc may be a marker of traits (trait marker). It seems, however, that the measurement of the concentrations of zinc might be in the future a component of the battery of tests; of markers of immune activation and oxidative stress rather than itself alone.  相似文献   
10.

BACKGROUND:

Breast cancers that are negative for the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 (human epidermal growth factor receptor 2) marker are more prevalent among African women, and the biologically aggressive nature of these triple‐negative breast cancers (TNBCs) may be attributed to their mammary stem cell features. Little is known about expression of the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) in African women. Novel data are reported regarding ALDH1 expression in benign and cancerous breast tissue of Ghanaian women.

METHODS:

Formalin‐fixed, paraffin‐embedded specimens were transported from the Komfo Anoyke Teaching Hospital in Kumasi, Ghana to the University of Michigan for centralized histopathology study. Expression of ER, PR, HER2, and ALDH1 was assessed by immunohistochemistry. ALDH1 staining was further characterized by its presence in stromal versus epithelial and/or tumor components of tissue.

RESULTS:

A total of 173 women contributed to this study: 69 with benign breast conditions, mean age 24 years, and 104 with breast cancer, mean age 49 years. The proportion of benign breast conditions expressing stromal ALDH1 (n = 40, 58%) was significantly higher than those with cancer (n = 44, 42.3%) (P = .043). Among the cancers, TNBC had the highest prevalence of ALDH1 expression, either in stroma or in epithelial cells. More than 2‐fold higher likelihood of ALDH1 expression was observed in TNBC cases compared with other breast cancer subtypes (odds ratio = 2.38, 95% confidence interval 1.03‐5.52, P = .042).

CONCLUSIONS:

ALDH1 expression was higher in stromal components of benign compared with cancerous lesions. Of the ER‐, PR‐, and HER2‐defined subtypes of breast cancer, expression of ALDH1 was highest in TNBC. Cancer 2013. © 2012 American Cancer Society.  相似文献   
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