首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   8108篇
  免费   1127篇
  国内免费   506篇
耳鼻咽喉   128篇
儿科学   27篇
妇产科学   208篇
基础医学   1280篇
口腔科学   374篇
临床医学   452篇
内科学   781篇
皮肤病学   81篇
神经病学   412篇
特种医学   179篇
外国民族医学   5篇
外科学   1046篇
综合类   1298篇
现状与发展   2篇
预防医学   144篇
眼科学   67篇
药学   439篇
  1篇
中国医学   194篇
肿瘤学   2623篇
  2024年   34篇
  2023年   180篇
  2022年   435篇
  2021年   545篇
  2020年   461篇
  2019年   391篇
  2018年   359篇
  2017年   424篇
  2016年   433篇
  2015年   565篇
  2014年   598篇
  2013年   550篇
  2012年   501篇
  2011年   516篇
  2010年   362篇
  2009年   402篇
  2008年   391篇
  2007年   326篇
  2006年   319篇
  2005年   287篇
  2004年   248篇
  2003年   173篇
  2002年   166篇
  2001年   138篇
  2000年   118篇
  1999年   115篇
  1998年   100篇
  1997年   81篇
  1996年   77篇
  1995年   69篇
  1994年   71篇
  1993年   47篇
  1992年   35篇
  1991年   34篇
  1990年   28篇
  1989年   17篇
  1988年   19篇
  1987年   18篇
  1986年   12篇
  1985年   21篇
  1984年   14篇
  1983年   6篇
  1982年   17篇
  1981年   9篇
  1980年   12篇
  1979年   5篇
  1978年   2篇
  1977年   6篇
  1976年   2篇
  1967年   1篇
排序方式: 共有9741条查询结果,搜索用时 78 毫秒
1.
Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.  相似文献   
2.
Abstract

Oxidative stress (OS) has been proposed to play a role in the development of EMs. Peroxiredoxins are a family of antioxidant proteins that exhibit peroxidase activity in a thioredoxin-dependent manner, protecting cells against OS. The Western blotting results showed that the relative expression of PRDX4 was significantly increased in ectopic endometria compared with the normal endometria of EMs-free (p?<?.05). The H2O2 concentration was also significantly higher in the ectopic endometrium. PRDX4 siRNA was transfected into primary ectopic endometrial stromal cells (EESCs). The viability of the transfected EESCs was measured by CCK-8 assay, and the results showed significantly decreased cell viability. Furthermore, the apoptosis rate and ROS generation in flow cytometry assays were significantly increased after the knockdown of PRDX4 expression (p?<?.05). Scratch assays and transwell assays revealed that decreased expression of PRDX4 mediated by siRNA inhibited EESC migration and invasion. In conclusion, these findings indicate the potential role of PRDX4 in the development of EMs and PRDX4 as a possible therapeutic target for EMs treatment.  相似文献   
3.
目的:探讨吉西他滨联合西妥昔单抗对三阴乳腺癌细胞增殖、迁移、侵袭的影响,并对可能的机制进行初步的探究。方法:将实验分为西妥昔单抗组(150 μg · mL-1)、吉西他滨联合用药组(西妥昔单抗150 μg · mL-1,吉西他滨2.8 μg·mL-1)。通过MTT、Transwell实验检测联合用药对MDA-MB-231细胞增殖、迁移、侵袭能力的影响,Western blotting实验检测合用药对MDA-MB-231细胞MMP-9、TIMP-1、p-IkB、NF-kB-p65表达水平的影响。结果:吉西他滨联合西妥昔单抗作用MDA-MB-231细胞后,其生长被不同程度的抑制,抑制率随吉西他滨浓度的增加而增高(P<0.05);联合用药组MDA-MB-231细胞迁移、侵袭数目明显减少(P<0.05),同时MMP-9、p-IkB、NF-kB-p65的表达含量降低,TIMP-1表达含量增加。结论:吉西他滨联合西妥昔单抗对三阴乳腺癌细胞增殖、侵袭、迁移具有抑制作用,并明显抑制MMP-9的表达,其机制可能是通过抑制NF-kB通路实现。  相似文献   
4.
5.

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Objective

To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies.

Design, setting, and participants

A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified.

Outcome measurements and statistical analyses

Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated.

Results and limitations

Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC).

Conclusions

Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting.

Patient summary

We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.  相似文献   
6.
目的:探讨血管生成、细胞增殖指数、DNA倍性在胰腺导管癌发生、发展中的作用及临床意义。方法:对29例胰腺导管癌和7例慢性胰腺炎患者的石蜡包埋标本作苏木精鄄伊红(HE)染色,CD34、Ki67免疫组织化学染色,镜下计算微血管密度(MVD)及Ki67阳性细胞比例,同时用流式细胞仪(FCM)检测细胞核DNA倍性,计算异倍体出现率及S期比例,并结合临床病理资料对各项指标作相关分析。结果:胰腺导管癌和慢性胰腺炎都有较多的新生血管。MVD值在胰腺导管癌高、中、低分化3组之间差异无显著性。按肿瘤直径分为≤1.5cm、1.6~2.9cm、≥3cm3组,此3组间MVD值、Ki67阳性细胞百分率、DNA异倍体出现率及肿瘤周围有无浸润的差异都非常显著(P<0.01)。肿瘤越大,MVD值、Ki67阳性细胞百分率及DNA异倍体出现率越高。结论:胰腺导管癌的发生、发展伴血管生成和DNA合成增加,联合测定MVD、Ki67阳性细胞百分率、DNA倍型可能为胰腺导管癌临床预后预测提供辅助参考指标。  相似文献   
7.
目的:探讨nm23-H1基因转染对人胆管癌细胞系QBC939体外浸润能力的影响。方法:将含有全长nm23-H1 cDNA的真核表达载体通过脂腩体法转染人胆管癌细胞系。结果:转染成功的QBC939细胞,其nm23-Hl基因的mRNA、蛋白表达明显增加,转染nm23-H1基因的胆管癌细胞体外浸润能力下降,穿越matrigel的细胞数明显低于亲本QBC939细胞,代表浸润能力的IV型胶原酶(MMP-9)分泌量下降。结论:nm23-Hl基因可以抑制胆管癌细胞的体外浸润能力。  相似文献   
8.
The aim of this study was to define criteria for the selection of patients for percutaneous or open operations for the cure of drug-resistant trigeminal neuralgia (TN). Trigeminal percutaneous radiofrequency thermorhizotomy (TPRT) has an established place because of its safety in elderly patients, while microvascular decompression (MVD) has appeal in younger patients beause of its non-destructive nature and because it attacks what is believed to be the primary etiology of tic douloureux. Nevertheless, MVD is a successful operation only when true neurovascular conflict (NVC) is ascertained, rather than a simple arterial loop and neurovascular contract. Probably, many immediate failures and early relapses are the consequence of the inadequate patient selection for MVD on the presumption that this operation is in any case the ideal cure. The inadequate selection can be explained by the difficult preoperative diagnosis of NVC in the past. Indeed, angiography and computed tomography showed the neurovascular contact but not the size of compression. Fortunately, today magnetic resonance imaging is a reliable instrument to ascertain NVC. So, the diatribe between the supporters of percutaneous techniques and MVD can be concluded with the following: (1) percutaenous techniques are indicated for patients without demonstrated NVC (including patients with TN in multiple sclerosis) and in those with NVC if MVD is contraindicated by ill-health or refused by the informed patient; and (2) MVD is incated for patients with ascertained NVC who are in good health and who, informed of the surgical risk, favor this operation desiring no sensory deficit. Received: 23 June 2001 / Accepted in revised form: 24 August 2001  相似文献   
9.
MMP-9和TIMP-1表达失衡与乳腺癌浸润、转移的相关性   总被引:2,自引:0,他引:2  
目的 研究乳腺癌组织中基质金属蛋白酶(MMP-9)和金属蛋白酶组织抑制因子(TIMP-1)的表达变化与乳腺癌生物学行为及淋巴结转移的关系。方法 应用SP免疫组织化学方法检测85例乳腺癌组织MMP-9,TIMP-1及细胞增殖核抗原ki-67的表达情况。结果 MMP-9阳性染色率90.59%,MMP-9阳性表达与肿瘤浸润,淋巴结转移,ki-67指数及TNM分期呈正相关(Pearson列联系数分别为P=0.03,P=0.02,P=0.004和P=0.0000,P<0.05,0.01。TIMP-1阳性染色率为78.82%,TIMP-1阳性表达与肿瘤浸润,淋巴结转移及TNM分期浸润,转移及ki-67指数显著相关(P<0.05,P<0.01,P<0.001)。结论 MMP-9和TIMP-1表达失衡与乳腺癌浸润及淋巴结转移密切相关。  相似文献   
10.
本文研究成骨肉瘤OS-732细胞系浸润软骨的机理,指出经盐酸胍处理后的软骨可被瘤细胞所浸润,这些浸润细胞在电镜下见其有生长、代谢旺盛的特点,提示正常软骨内含有抑制肿瘤细胞浸润的因子存在。  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号