全文获取类型
收费全文 | 13100篇 |
免费 | 1157篇 |
国内免费 | 1273篇 |
专业分类
儿科学 | 28篇 |
妇产科学 | 54篇 |
基础医学 | 800篇 |
口腔科学 | 4篇 |
临床医学 | 965篇 |
内科学 | 3660篇 |
皮肤病学 | 15篇 |
神经病学 | 28篇 |
特种医学 | 299篇 |
外科学 | 3343篇 |
综合类 | 1476篇 |
预防医学 | 542篇 |
眼科学 | 2篇 |
药学 | 671篇 |
3篇 | |
中国医学 | 183篇 |
肿瘤学 | 3457篇 |
出版年
2024年 | 25篇 |
2023年 | 236篇 |
2022年 | 575篇 |
2021年 | 706篇 |
2020年 | 634篇 |
2019年 | 519篇 |
2018年 | 506篇 |
2017年 | 377篇 |
2016年 | 589篇 |
2015年 | 624篇 |
2014年 | 1151篇 |
2013年 | 941篇 |
2012年 | 884篇 |
2011年 | 841篇 |
2010年 | 740篇 |
2009年 | 769篇 |
2008年 | 800篇 |
2007年 | 828篇 |
2006年 | 672篇 |
2005年 | 581篇 |
2004年 | 432篇 |
2003年 | 323篇 |
2002年 | 299篇 |
2001年 | 257篇 |
2000年 | 243篇 |
1999年 | 188篇 |
1998年 | 118篇 |
1997年 | 134篇 |
1996年 | 87篇 |
1995年 | 89篇 |
1994年 | 61篇 |
1993年 | 46篇 |
1992年 | 36篇 |
1991年 | 28篇 |
1990年 | 32篇 |
1989年 | 29篇 |
1988年 | 28篇 |
1987年 | 28篇 |
1986年 | 20篇 |
1985年 | 19篇 |
1984年 | 15篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1977年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
目的:探讨血小板活化因子(PAF)、癌胚抗原(CEA)、糖类抗原724(CA-724)在结直肠癌(CRC)患者术前血清中的阳性表达率及与临床病理特征的关系、发病的独立危险因素。方法:选取2019年12月至2021年10月于包头医学院第一附属医院就诊的CRC患者75例为CRC组,另选取同时期在本院体检的健康志愿者75例为对照组。采用酶联免疫吸附(ELISA)法分别检测CRC患者术前及对照组的晨空腹外周静脉血PAF含量;回顾性分析上述入组患者术前血清CEA、CA-724含量,进行统计分析。结果:(1)CRC组PAF、CEA、CA-724单独检测和联合检测的阳性率分别为25.33%、42.67%、30.67%、74.67%,均高于对照组,且联合检测的阳性率均高于单独检测指标的阳性率,组间差异均具有统计学意义(P<0.05);(2)单因素方差分析结果显示,血清CEA表达水平的影响因素为患者的淋巴结转移(P<0.05);血清CA-724表达水平的影响因素为患者的年龄(P<0.05);(3)二元Logistic回归分析结果显示,PAF表达在临床病理特征之间的差异无统计学意义(P&... 相似文献
72.
转录因子Ascl2作为WNT信号靶基因,可影响结直肠癌(CRC)前体细胞干性特征,探讨其能否调控短链脂肪酸β-氧化而影响CRC患者的预后。方法 下载稳定干扰Ascl2表达的CRC LS174T细胞(sh-Ascl2/LS174T)的mRNA及miRNA差异表达数据(GSE69036和GSE34926)分析其靶基因;应用RT-PCR方法和Western 印迹定量检测sh-Ascl2/LS174T及对照细胞中的Ascl2、Acss1和Acss3的mRNA表达水平,以及Ascl2和Acss1蛋白表达水平,从GSE44076表达数据和UALCAN数据比较在正常结直肠粘膜、CRC组织和不同临床病理分期的肿瘤组织的表达水平差异;TCGA数据库下载548例CRC患者基因 mRNA表达量及相关临床信息,用Spearman等级相关分析表达相关性,Kaplan-Meier法进行生存分析,Cox回归分析评估危险因素。结果 sh-Ascl2/LS174T细胞中Acss1的mRNA较对照细胞下调2.08倍,miR-4282表达水平下调2.069倍。RT-PCR定量检测sh-Ascl2/LS174T细胞中Acss1的mRNA和miR-4282水平明显下降(P<0.01), Acss3的mRNA水平明显升高(P<0.05);Acss1和Ascl2蛋白水平较对照细胞均明显下降。CRC组织Ascl2和Acss1的mRNA水平明显高于癌旁结直肠粘膜组织(P<0.001),而Acss3明显低于癌旁结直肠粘膜组织 (P<0.001);CRC组织中Ascl2与Acss1的mRNA表达水平呈正相关,与Acss3的表达水平呈负相关(均P<0.001)。Ascl2和Acss3表达水平与疾病特异性生存期(DSS)、总体生存期(OS)、无进展生存期(PFS)无关,Acss1高表达组比低表达组的DSS (P=0.0389)和OS (P=0.04)明显降低。Ascl2与Acss1基因异常表达、Ascl2、Acss1和Acss3基因异常联合表达与CRC患者的DSS存在显著的联系(P=0.0377和P=0.0161),Ascl2、Acss1和Acss3三个基因的联合异常表达是影响CRC患者DSS的危险因素之一(P=0.043)。结论Ascl2对CRC细胞中的Acss1/3的表达可能具有调控作用而导致其短链脂肪酸β-氧化的重编程,它们的联合异常表达可以一定程度预测CRC患者的预后 相似文献
73.
目的:设计并筛选能有效抑制人肝癌SMMC-7721细胞、人结肠癌Caco2细胞、人胃癌SCG-7901细胞增殖的增殖细胞核抗原(PCNA) siRNA。方法:总结以往提出的siRNA 设计原则的基础上,设计4 条PCNA siRNA,体外转录合成PCNA siRNA;并作用于3 种肿瘤细胞,WST-8法检测细胞增殖活性,筛选能有效抑制肿瘤细胞增殖的siRNA序列;RT-PCR检测细胞PCNA mRNA水平;免疫细胞化学方法检测 PCNA 蛋白表达水平。结果:4 条PCNA siRNA中,有3 条序列(No.2、No.4、No.3)的siRNA能有效抑制3 种肿瘤细胞的增殖;其中No.2、No.4作用效果最优,以50 nmol/L浓度作用48 h,对3种肿瘤细胞的增殖抑制率均可达到62%以上,No.2、No.4 PCNA siRNA均能在mRNA和蛋白水平显著下调PCNA的表达。结论:PCNA siRNA能在体外有效抑制SMMC-7721细胞、Caco2细胞、SCG-7901细胞的增殖,其适宜作用浓度为50 nmol/L,适宜作用时间为48 h。 相似文献
74.
Wafaa M. Elzefzafy Soheir Abd Elrahman Nesreen Atef 《Journal of immunoassay & immunochemistry》2020,41(4):729-744
ABSTRACT
Background
Colorectal cancer (CRC) is considered a major cause of morbidity and mortality in Egypt. Colonoscopy is the standard for detection of lesions. The combination of screening methods is effective. Decrease and loss of DPP-IV/CD26 expression and activity are found in microenvironments of specific tumors which are related to impaired immune functions. 相似文献75.
Nae Yu Kim Jung-Soo Pyo Dong-Wook Kang Seung-Min Yoo 《Pathology, research and practice》2019,215(3):580-585
Objective
The aim of this study was to elucidate the clinicopathological significance and prognostic role of loss of claudin-1 in colorectal cancer (CRC).Methods
The correlations between claudin-1 expression and clinicopathological characteristics, including survival rates, were assessed using immunohistochemistry on 260 archival, paraffin-embedded CRC tissues. In addition, the correlations between cludin-1 and nuclear factor-kappa B (NF-κB), epithelial-mesenchymal transition markers and tumor-infiltrating lymphocytes were investigated.Results
Claudin-1 expression was markedly lost in 42.7% of the 260 CRCs analyzed. Loss of claudin-1 expression significantly correlated with larger tumor size, vascular invasion, higher pT stage, and high metastatic lymph node ratio. In addition, loss of claudin-1 expression significantly correlated with NF-κB activation (P?<?0.001), high SNAI (P?<?0.001), and low E-cadherin (P?<?0.001) expressions. Patients with high immunoscores showed significantly lower rates of claudin-1 expression loss (P?=?0.020). In detail, loss of claudin-1 expression were frequently found in CRCs low CD3- and CD8-positive lymphocytes. There were significant correlations between claudin-1 expression loss and poor overall and recurrence-free survivals (P?<?0.001 and P?<?0.001, respectively).Conclusion
Taken together, our results suggest that the loss of claudin-1 expression significantly correlates with aggressive tumor behaviors, high SNAI expression, lower immunoscore, and poor prognoses. 相似文献76.
How many lymph nodes are necessary to stage early and advanced adenocarcinoma of the sigmoid colon and upper rectum? 总被引:5,自引:0,他引:5
Leibl S Tsybrovskyy O Denk H 《Virchows Archiv : an international journal of pathology》2003,443(2):133-138
The lymph-node yields in specimens resected for colorectal adenocarcinoma show considerable variations, raising the question whether the minimum lymph-node number recommended by the UICC (International Union Against Cancer) for pN0 classification represents an appropriate quality standard for specimen work-up. The number of pericolic lymph nodes recovered from 568 archival surgical colorectal carcinoma specimens located in the sigmoid or upper rectum showed a highly statistically significant correlation with both the pT category and the presence of metastases (P<0.0005). The median lymph-node yield in standardized (i.e., resembling in size surgically removed cancer specimens) tumor-free specimens obtained during autopsies was 13 lymph nodes, compared with 20.5 when diverticula were present and more than 30 in specimens with chronic inflammation or from patients with systemic infections. In 48 pT2 and pT3 carcinoma specimens prospectively dissected in the same way, median numbers of 18 (pT2) and 23 (pT3) lymph nodes were detected (range between 8 and 39 nodes). The lymph-node numbers recommended in previous studies and by the UICC often seem to be too low to declare a specimen free of metastases. Although the great variation in lymph-node counts requires the recovery of all lymph nodes for pN0 classification, recommendations considering the pT status and additional factors like diverticula and inflammatory changes can be useful as a quality standard for specimen work up. 相似文献
77.
目的:研究树突状细胞(DCs)激活的细胞毒性T细胞的抗肿瘤及预防肿瘤发生的作用。 方法: 细胞因子诱生人PBMC未成熟DCs,加入肿瘤细胞抗原提取物致敏DCs产生成熟DCs;通过细胞形态、表面标记鉴定成熟DCs,MTT法测成熟DCs活化的细胞毒性T细胞(CTL)的体外杀伤活性;裸鼠体内注射活化CTL观察其抑制移植瘤生长及发生的作用。 结果: 经过7 d培养,获得大量形态典型、具有强烈刺激增殖能力、高表达CD80(63.5%)、CD83(67.6%)和CD3/ HLA-DR(83.2%)的DCs。其活化的CTL在20∶1效靶比时对抗原来源细胞株自身的杀伤率达75%以上,对同系细胞株的杀伤活性为35%-45%,对其它种系肿瘤细胞仅有微弱杀伤力(P<0.01)。CTL对裸鼠结肠癌HT-29移植瘤有特异性的生长抑制和预防生成作用(P<0.05)。CTL治疗组肿瘤组织中PCNA表达水平显著低于对照组(P<0.05)。 结论: 肿瘤细胞抗原活化的DC诱导CTL对肿瘤有特异性的杀伤作用,体内应用可特异性抑制移植结肠癌的生长或预防小鼠结肠癌移植瘤的发生。 相似文献
78.
Guido Monga Gianna Mazzucco Francesco Paolo Rossini Franco Presti 《Virchows Archiv : an international journal of pathology》1979,382(3):355-360
Summary An unusual form of colorectal polyposis is described displaying juvenile, adenomatous and mixed patterns in a 17-year-old girl. Although juvenile polyposis is generally considered to be non-neoplastic in nature, in both the present and in other case reports histological findings support a neoplastic nature. Since an increase in the incidence of large bowel carcinomas has been found in subjects with a previous diagnosis of juvenile polyposis, these patients should be considered to be at risk, and submitted to follow up. 相似文献
79.
del Ara RM González-Polo RA Caro A del Amo E Palomo L Hernández E Soler G Fuentes JM 《Clinical and experimental medicine》2002,2(1):53-57
Arginase activity was measured in serum and biopsy from healthy individuals and colorectal cancer patients. Arginase activity
in tumor samples (87±7.7 U/g tissue) was significantly higher than in controls (40.7±3.3 U/g tissue). However, serum arginase
activity did not show any significant change in both groups. Finally, the micromethod used to quantify arginase activity in
this study is superior to other methods because it has increased sensitivity, requires less sample, and is less time-consuming.
Arginase differences are significant, according to the t-test (P<0.05).
Received: 14 September 2001 / Accepted: 6 February 2002 相似文献
80.
目的:探讨DNA启动子区5′CpG岛甲基化状态与人结肠癌RKO细胞增殖凋亡等生物学特征的关系。方法: 应用特异性DNA甲基转移酶(DNMTs)抑制剂-5-氮-2′-脱氧胞苷(5-Aza-2′-deoxycytidine,5-Aza-CdR)处理肠癌RKO细胞72 h,甲基化特异性PCR(methylation-specific PCR,MSP)及DNA测序法分析p16/CDKN2基因CpG岛甲基化状态;MTT、FCM、荧光染色及透射电镜检测启动子区去甲基化后细胞生长、形态和细胞周期凋亡的影响。 结果: DNMTs抑制剂能较好地逆转启动子区胞嘧啶甲基化状态;CpG岛去甲基化后能明显地抑制肠癌细胞的生长,增加细胞群体倍增时间(P<0.01),诱导肠癌细胞凋亡,影响肠癌细胞周期分布,并具有良好的量效依赖关系。 结论: 通过逆转CpG岛高甲基化能有效地抑制肠癌细胞增殖,为临床治疗大肠癌提供新的作用靶点。 相似文献