全文获取类型
收费全文 | 74804篇 |
免费 | 7194篇 |
国内免费 | 5567篇 |
专业分类
耳鼻咽喉 | 771篇 |
儿科学 | 774篇 |
妇产科学 | 648篇 |
基础医学 | 7424篇 |
口腔科学 | 1123篇 |
临床医学 | 9442篇 |
内科学 | 9478篇 |
皮肤病学 | 714篇 |
神经病学 | 3522篇 |
特种医学 | 2885篇 |
外国民族医学 | 39篇 |
外科学 | 8178篇 |
综合类 | 16025篇 |
现状与发展 | 18篇 |
一般理论 | 4篇 |
预防医学 | 5798篇 |
眼科学 | 1858篇 |
药学 | 8243篇 |
79篇 | |
中国医学 | 4618篇 |
肿瘤学 | 5924篇 |
出版年
2024年 | 283篇 |
2023年 | 1186篇 |
2022年 | 3294篇 |
2021年 | 3804篇 |
2020年 | 2912篇 |
2019年 | 2127篇 |
2018年 | 2435篇 |
2017年 | 2509篇 |
2016年 | 2259篇 |
2015年 | 3616篇 |
2014年 | 4486篇 |
2013年 | 4362篇 |
2012年 | 6392篇 |
2011年 | 6898篇 |
2010年 | 4902篇 |
2009年 | 4013篇 |
2008年 | 4702篇 |
2007年 | 4529篇 |
2006年 | 4214篇 |
2005年 | 3684篇 |
2004年 | 2499篇 |
2003年 | 2147篇 |
2002年 | 1734篇 |
2001年 | 1374篇 |
2000年 | 1328篇 |
1999年 | 1149篇 |
1998年 | 747篇 |
1997年 | 667篇 |
1996年 | 476篇 |
1995年 | 472篇 |
1994年 | 374篇 |
1993年 | 251篇 |
1992年 | 287篇 |
1991年 | 285篇 |
1990年 | 203篇 |
1989年 | 171篇 |
1988年 | 166篇 |
1987年 | 166篇 |
1986年 | 125篇 |
1985年 | 87篇 |
1984年 | 75篇 |
1983年 | 40篇 |
1982年 | 33篇 |
1981年 | 22篇 |
1980年 | 11篇 |
1979年 | 27篇 |
1978年 | 9篇 |
1974年 | 10篇 |
1972年 | 6篇 |
1969年 | 3篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Jianwei Yang Yan Meng Ying Su Zeng Chen Wei Gao Jinyuan Lin Jing Jia Huamei Lin 《中德临床肿瘤学杂志》2014,(10):451-456
Objective: The aim of the study was to investigate the relationship between susceptibility of paclitaxel-based regimen and gene polymorphisms of cytochrome oxidase CYP3A4 for advanced gastric cancer. Methods: Peripheral venous blood sample of 53 advanced gastric cancer patients were enrolled to test the mutation of CYP3A4 gene by denaturing high performance liquid chromatography(DHPLC) and DNA sequencing. The relation between the efficacy of paclitaxel-based regimen and CYP3A4 gene polymorphisms was further analyzed. Results: DHPLC indicated that among the 53 patients, 21 cases showed biomodal type(mutation) and 32 cases were of unimodal type(wild-type). Sequencing results showed that the deletion mutation was found at the 27 th basic group of C in exon 10 of CYP3A4 gene. The response rate(RR) and disease control rate(DCR) of wild-type group were 40.6% and 84.4%, while in mutation group they were 33.3% and 85.7%, respectively, with no significances between the two groups(P 0.05). Of all 53 cases, the median progression-free survival(PFS) was 6.5 months(95% CI: 3.576–9.424 months), and the median overall survival(OS) was 11.0 months(95% CI: 6.955–15.045 months). The median PFS and OS in wild-type group had no differences compared with those in mutation group(7.0 months vs. 7.0 months, P 0.05; 10.0 months vs. 14.0 months, P 0.05). Between wild-type and mutation groups, the median PFS of patients applied with oxaliplatin containing regimen and the median OS in patients applied with/without oxaliplatin had no significant differences(P 0.05), while the median PFS in patients received non-oxaliplatin regime had statistical differences(P = 0.024). The median PFS and OS in patients receiving 3-drug or 2-drug regimes had no correlation with CYP3A4 gene polymorphisms. The adverse effects in the two groups were mild, mainly in grades 1–2. The common adverse effects were anorexia, nausea/vomiting and leucopenia. Conclusion: Deletion mutation was located in 相似文献
992.
目的:研究YAP在骨肉瘤细胞中的表达情况和定位。方法:使用SOSP9607、MG63、U2-OS骨肉瘤细胞系和hFOB1.19成骨细胞系,进行qRT-PCR、Western blot实验和荧光共聚焦显微镜观察YAP的表达情况和所在的具体细胞位置。结果:YAP在骨肉瘤细胞中表达量非常高,高于正常的成骨细胞hFOB1.19。YAP在骨肉瘤细胞系中主要表达于细胞核内,而在成骨细胞系中主要表达于细胞质。结论:YAP在骨肉瘤细胞中高表达,在成骨细胞中低表达。在肿瘤细胞中主要位于细胞核内,而在成骨细胞系中主要表达于胞质内。可以推断YAP进入细胞核内,结合下游靶基因,促进肿瘤细胞的生长,参与骨肉瘤细胞的发生。这一发现可以为治疗骨肉瘤提供新的靶点。 相似文献
993.
目的:探讨新疆维吾尔族(维族)和汉族胃癌患者肿瘤坏死因子-α基因(TNF-A)rs1800629和rs361525位点多态性及其单体型与胃癌易感性的关系。方法:采用Snapshot技术分析322例胃癌患者(其中维族93例,汉族229例)和作为对照的487例非胃癌患者(其中维族231例,汉族256例)TNF-A基因rs1800629和rs361525位点基因型的分布;利用SHEsis软件分析其构成的单体型在病例组和对照组中的分布频率,比较基因型和单体型在病例组和对照组间的分布差异。结果:在维族人群中,TNF-A基因rs1800629和rs361.525位点不论是等位基因位点、基因型还是单体型在病例组和对照组中的分布频率差异均无统计学意义(P>0.05)。在汉族人群中,TNF-A基因rs361525位点AA+GA基因型在病例组和对照组之间的分布差异有统计学意义(χ=4.56,P=0.03),即携带A等位基因者发生胃癌的风险增加(OR=2.41,95%CI:1.06~5.49);rs1800629位点基因型与胃癌之间未发现明显关联;A-A单体型在病例组及对照组分布频率分别为0.92%和0.86%,差异有统计学意义(χ~2=7.03,P=0.01)。结论:TNF-A基因单核苷酸多态性与汉族人群胃癌发病风险相关,这种相关性具有民族差异。 相似文献
994.
目的:探讨预后营养指数(PNI)对腹腔镜直肠癌根治术后并发症的预测价值。方法:回顾性分析2016年1月至2020年5月在我院普外科行腹腔镜直肠癌根治术的220例直肠癌患者的临床资料。根据术后有无发生并发症分为并发症组(n=63例)和无并发症组(n=157例)。比较两组临床病理特征;采用多因素Logistic回归分析影响腹腔镜直肠癌根治术后并发症的危险因素。结果:220例接受腹腔镜直肠癌根治术患者中63例(28.64%)术后发生了并发症;两组年龄、性别、BMI、术前有合并疾病、肿瘤位置、TNM分期、肿瘤直径、手术时间、PNI组间比较差异有统计学意义(P<0.05);多因素Logistic回归分析显示,年龄、性别、术前合并疾病、肿瘤位置、手术时间和PNI是腹腔镜直肠癌根治术后并发症发生的独立危险因素(P<0.05)。结论:术前低PNI是腹腔镜直肠癌根治术后并发症的独立危险因素,临床上可通过PNI评估患者术前营养状况,必要时术前予以营养支持治疗。 相似文献
995.
目的:沉默肺癌细胞系A549的程序性死亡配体1(programmed death ligand 1,PD-L1)基因,观察其对A549细胞增殖和凋亡的影响。方法:构建PD-L1 shRNA重组质粒p GPU6/PD-L1,并应用脂质体转染法将其转染入A549细胞。RT-PCR法检测PD-L1基因的表达;Western blotting法检测PD-L1蛋白的表达;MTT法检测p GPU6/PD-L1对A549细胞增殖的影响;AnnexinⅤ-FITC/PI双染法检测p GPU6/PD-L1对A549细胞凋亡的影响。结果:成功将p GPU6/PD-L1转染入A549细胞;RT-PCR结果显示p GPU6/PD-L1使A549细胞PD-L1基因表达水平降低;Western blotting结果显示p GPU6/PD-L1转染A549细胞使PDL1蛋白表达减少;MTT结果显示p GPU6/PD-L1能够抑制A549细胞增殖;AnnexinⅤ-FITC/PI双染法检测结果显示p GPU6/PD-L1能够诱导A549细胞凋亡。结论:p GPU6/PD-L1能够下调肺癌细胞A549 PD-L1的表达,抑制细胞增殖,并诱导细胞凋亡。 相似文献
996.
Su J Zhang A Shi Z Ma F Pu P Wang T Zhang J Kang C Zhang Q 《International journal of oncology》2012,40(4):1162-1170
The Wnt/β-catenin signaling pathway is crucial for human organ development and is involved in tumor progression of many cancers. Accumulating evidence suggests that the expression of β-catenin is, in part, regulated by specific microRNAs (miRNAs). The purpose of this study was to determine the expression of a recently identified epithelial to mesenchymal transition (EMT)-associated tumor suppressor microRNA (miR)-200a, in cancer cells. We also aimed to identify specific miR-200a target genes and to investigate the antitumor effects of miR-200a on the Wnt/β-catenin signaling pathway. We employed TOP/FOP flash luciferase assays to identify the effect of miR-200a on the Wnt/β-catenin pathway and we confirmed our observations using fluorescence microscopy. To determine target genes of miR-200a, a 3' untranslated region (3' UTR) luciferase assay was performed. Cell viability, invasion and wound healing assays were carried out for functional analysis after miRNA transfection. We further investigated the role of miR-200a in EMT by Western blot analysis. We found fluctuation in the expression of miR-200a that was accompanied by changes in the expression of members of the Wnt/β-catenin signaling pathway. We also determined that miR-200a can directly interact with the 3' UTR of CTNNB1 (the gene that encodes β-catenin) to suppress Wnt/β-catenin signaling. MiR-200a could also influence the biological activities of SGC790 and U251 cells. Our results demonstrate that miR-200a is a new tumor suppressor that can regulate the activity of the Wnt/β-catenin signaling pathway via two mechanisms. MiR-200a is a candidate target for tumor treatment via its regulation of the Wnt/β-catenin signaling pathway. 相似文献
997.
We examined the promoter hypermethylation of tumor-suppressor genes RASSF1A and TSLC1, quantitated EBV DNA load in nasopharyngeal carcinoma (NPC) tissues (T tissues), and matched tumor-adjacent tissues outside 0.5 cm (P tissues) and outside 1.0 cm (Z tissues) to evaluate the role of promoter hypermethylation of RASSF1A and TSLC1 as well as viral load in the pathogenesis of NPC. Methylation-specific polymerase chain reaction (PCR) for RASSF1A and TSLC1 and quantitative real-time PCR analysis of EBV DNA were performed on matched T, P, and Z tissues (n = 28) as well as chronic nasopharyngitis tissues (n = 8). Hypermethylated RASSF1A was frequently detected in the T (82%) and P tissues (75%), but less frequently in Z tissues (46%). he average quantities of EBV DNA (copies/microg DNA) in matched T, P, and Z tissues were 673,000, 90,000, and 7000. The differences of promoter hypermethylation of RASSF1A and EBV viral load among T, P, and Z tissues were statistically significant, with more frequent methylation and higher viral load detected when tissues examined were nearer to the NPC tissues. Our results suggest that aberrant hypermethylation of RASSF1A and high EBV load might be important events in NPC pathogenesis, and they may be useful molecular diagnostic markers for this cancer. 相似文献
998.
目的 乳腺癌已成为世界范围内女性恶性肿瘤中最常见的死因,伴有钙化的乳腺癌占乳腺癌30%~50%.探讨伴有钙化的乳腺浸润性导管癌(invasive ductal carcinoma,IDC)的临床病理特征及预后的影响因素.方法 收集2012-06-01-2013-06-30新疆医科大学附属肿瘤医院收治的初治可手术女性乳腺癌患者307例的临床病理资料和随访资料,根据乳腺X射线图像特征分为钙化组与非钙化组,回顾性分析其临床病理特征及3年无病生存率(disease-free survival,DFS).结果 钙化组在病理类型(P<0.001)、淋巴结转移(P=0.037)、人表皮生长因子受体2(human epidermal growth fator gene-2,HER2)过表达(P=0.005),组织学分级(P=0.043)、临床分期(P=0.021)与非钙化组比较差异有统计学意义.钙化是淋巴结转移及HER2过表达的相关风险因素.钙化组淋巴结转移的风险是非钙化组的1.736倍;钙化组HER2过表达的风险是非钙化组的2.297倍.钙化组和非钙化组3年DFS分别为87.5%和94.9%.肿瘤直径(P=0.025)和淋巴结(P=0.009)是影响乳腺IDC无病生存时间的独立预后因素.结论 钙化组乳腺IDC更具有肿瘤转移性,预后较非钙化组差. 相似文献
999.
Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain 下载免费PDF全文
Zhuofeng Ding Wei Xu Jie Zhang Wangyuan Zou Qulian Guo Changsheng Huang Chang Liu Tao Zhong Jun‐Ming Zhang Zongbin Song 《International journal of cancer. Journal international du cancer》2017,140(2):411-422
Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line‐derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states. 相似文献
1000.
Tumor‐suppressive miR‐145 co‐repressed by TCF4‐β‐catenin and PRC2 complexes forms double‐negative regulation loops with its negative regulators in colorectal cancer 下载免费PDF全文