全文获取类型
收费全文 | 19177篇 |
免费 | 2516篇 |
国内免费 | 663篇 |
专业分类
22356篇 |
出版年
2024年 | 135篇 |
2023年 | 678篇 |
2022年 | 962篇 |
2021年 | 1473篇 |
2020年 | 1412篇 |
2019年 | 2022篇 |
2018年 | 1310篇 |
2017年 | 905篇 |
2016年 | 825篇 |
2015年 | 997篇 |
2014年 | 1547篇 |
2013年 | 1861篇 |
2012年 | 840篇 |
2011年 | 986篇 |
2010年 | 547篇 |
2009年 | 697篇 |
2008年 | 628篇 |
2007年 | 642篇 |
2006年 | 610篇 |
2005年 | 505篇 |
2004年 | 407篇 |
2003年 | 364篇 |
2002年 | 310篇 |
2001年 | 189篇 |
2000年 | 175篇 |
1999年 | 154篇 |
1998年 | 154篇 |
1997年 | 108篇 |
1996年 | 119篇 |
1995年 | 111篇 |
1994年 | 89篇 |
1993年 | 86篇 |
1992年 | 95篇 |
1991年 | 70篇 |
1990年 | 40篇 |
1989年 | 39篇 |
1988年 | 48篇 |
1987年 | 42篇 |
1986年 | 28篇 |
1985年 | 40篇 |
1984年 | 31篇 |
1983年 | 8篇 |
1982年 | 15篇 |
1981年 | 9篇 |
1980年 | 14篇 |
1979年 | 10篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1970年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
931.
目的:观察近端胃切除和全胃切除对近端胃癌的疗效。方法:比较28例患有早期近端胃癌接受近端胃切除28例患者与100例患有早期近端胃癌接受全胃切除的患者,观察近端胃切除是否优于全胃切除。结果:两种治疗方法手术时间、术后并发症(包括吻合口瘘)没有差异。两组患者胃切除后的代谢变化结果相似,体重,血清血红蛋白以及血清总蛋白浓度变化相近。近端胃切除后腹泻(32%)和胃食管返流(28%)最为常见,而全胃切除后餐后腹胀(21%)最为常见。二者的术后5年生存率没有明显差别。结论:近端胃切除不会由于残余胃的生理优势而优于全胃切除术。 相似文献
932.
目的:建立雌/孕激素受体(ER/PR)阴性和阳性乳腺癌的蛋白质表达谱,寻找ER/PR阴性和阳性乳腺癌中差异表达蛋白,为乳腺癌患者提供新的预后预测指标和治疗新靶点。方法:应用蛋白质组学i TRAQ技术建立ER/PR阳性和阴性乳腺癌的蛋白质差异表达谱,鉴定两组乳腺癌的差异表达蛋白,对部分差异表达蛋白进行生物信息学分析,包括蛋白功能注释和分类GO分析和KEGG通路分析。结果:应用i TRAQ蛋白质组学技术对乳腺癌组织进行了蛋白组学分析,鉴定出ER/PR阳性和阴性组间有差异表达的蛋白4999种,以ER/PR阳性:ER/PR阴性≥3为上调标准,确定ER/PR阳性组上调蛋白101种。以ER/PR阳性:ER/PR阴性≤0.5为下调标准,ER/PR阳性组下调蛋白122种。GO分析结果显示ER/PR受体阴性和阳性乳腺癌的差异表达蛋白的分子功能、生物过程、细胞定位较为复杂,并且在上调蛋白和下调蛋白上存在分布差异。KEGG通路分析发现部分差异表达蛋白涉及201条信号通路。结论:ER/PR阳性和阴性乳腺癌间存在差异表达蛋白,这些蛋白涉及复杂的分子功能、生物过程和信号通路。 相似文献
933.
Jakub Karczmarski Tymon Rubel Agnieszka Paziewska Michal Mikula Mateusz Bujko Paulina Kober Michal Dadlez Jerzy Ostrowski 《Clinical proteomics》2014,11(1):24
Background
Histone post-translational modifications (PTMs) play an important role in the regulation of the expression of genes, including those involved in cancer development and progression. However, our knowledge of PTM patterns in human tumours is limited.Methods
MS-based analyses were used to quantify global alterations of histone PTMs in colorectal cancer (CRC) samples. Histones isolated from 12 CRCs and their corresponding normal mucosa by acidic extraction were separated by SDS-PAGE and analysed by liquid chromatography-mass spectrometry.Results
Among 96 modified peptides, 41 distinct PTM sites were identified, of which 7, 13, 11, and 10 were located within the H2A, H2B, H3, and H4 sequences, respectively, and distributed among the amino-terminal tails and the globular domain of the four histones. Modification intensities were quantified for 33 sites, of which 4 showed significant (p-value ≤ 0.05) differences between CRC tissues and healthy mucosa samples. We identified histone H3 lysine 27 acetylation (H3K27Ac) as a modification upregulated in CRC, which had not been shown previously.Conclusions
The present results indicate the usefulness of a bottom-up proteomic approach for the detection of histone modifications at a global scale. The differential abundance of H3K27Ac mark in CRC, a PTM associated with active enhancers, suggests its role in regulating genes whose expression changes in CRC. 相似文献934.
VLJ Whitehall TD Dumenil DM McKeone CE Bond ML Bettington RL Buttenshaw L Bowdler GW Montgomery LF Wockner BA Leggett 《Epigenetics》2014,9(11):1454-1460
The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features. 相似文献
935.
《Cancer epidemiology》2014,38(3):286-290
PurposeThe group of luminal (Her2 negative) is distinguished from other subtypes of breast cancer. We aimed to produce a prognostic index specific for luminal (Her2 negative) subtype breast cancer that could assist clinical treatment.MethodsThe test set comprised 406 consecutive luminal (Her2 negative) breast cancer patients. The relationship of 11 clinicopathologic factors including survivin with the 5-year disease-free survival was analyzed.ResultsIn univariate analysis, TNM stage, surgery, tumor size, lymph node involvement, and survivin expression were prognostic factors. In multivariate analysis, tumor size [HR (95% CI): 1.98 (1.12–3.49), p = 0.019], the number of lymph node metastasis [HR (95% CI): 1.75 (1.33–2.29), p < 0.0001] and the expression of progesterone receptor [HR (95% CI): 0.58 (0.36–0.95), p = 0.029] can independently predict prognosis. Prognostic index (PI) was calculated as 0.68 × tumor size + 0.56 × the number of lymph node metastasis − 0.54 × PR. According to the PI, patients were categorized into three groups: low, middle, and high risk group with the 5-year disease-free survival rates of 91.91%, 84.97% and 70.47%, respectively (P < 0.001). In the validation set, the luminal prognostic index (LPI) remained significant.ConclusionThe LPI may be a useful tool for evaluating the outcome of patients with luminal (Her-2 negative) breast cancer. 相似文献
936.
Anand Bery Felix Leung Christopher R Smith Eleftherios P Diamandis Vathany Kulasingam 《Clinical proteomics》2014,11(1):13
Background
Conventional proteomic approaches have thus far been unable to identify novel serum biomarkers for ovarian cancer that are more sensitive and specific than the current clinically used marker, CA-125. Because endogenous peptides are smaller and may enter the circulation more easily than proteins, a focus on the low-molecular-weight region may reveal novel biomarkers with enhanced sensitivity and specificity. In this study, we deciphered the peptidome of ascites fluid from 3 ovarian cancer patients and 3 benign individuals (ascites fluid from patients with liver cirrhosis).Results
Following ultrafiltration of the ascites fluids to remove larger proteins, each filtrate was subjected to solid phase extraction and fractionated using strong cation exchange chromatography. The resultant fractions were analyzed using an Orbitrap mass spectrometer. We identified over 2000 unique endogenous peptides derived from 259 proteins. We then catalogued over 777 peptides that were found only in ovarian cancer ascites. Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin.Conclusions
Peptidomics may uncover previously undiscovered disease-specific endogenous peptides that warrant further investigation as biomarkers for ovarian cancer. 相似文献937.
大肠癌细胞GST-Pi免疫细胞化学的超微结构定位 总被引:2,自引:0,他引:2
探讨GST-Pi在大肠癌细胞内亚微结构定位及其与大肠癌发生的关系。应用免疫电镜技术(免疫胶体金法)对6例大肠腺癌及3例正常大肠粘膜细胞进行GST-Pi的定位观察。6例大肠癌细胞内均出现GST-Pi胶体金阳性颗粒,主要分布于胞浆的线粒体、溶酶体、近胞膜部位的胞头中,也分布在核内和核膜上。金颗粒呈团状、点灶状分布,图象清晰。3例正常粘膜细胞内未见GST-Pi的金颗粒阳性表达,结果表明,GST-Pi在癌细胞内的特异性表达可作为大肠癌的诊断指标之一。 相似文献
938.
Andrew M Kaz Chao-Jen Wong Slavomir Dzieciatkowski Yanxin Luo Robert E Schoen William M Grady 《Epigenetics》2014,9(4):492-502
Alterations in DNA methylation have been proposed to create a field cancerization state in the colon, where molecular alterations that predispose cells to transformation occur in histologically normal tissue. However, our understanding of the role of DNA methylation in field cancerization is limited by an incomplete characterization of the methylation state of the normal colon. In order to determine the colon’s normal methylation state, we extracted DNA from normal colon biopsies from the rectum, sigmoid, transverse, and ascending colon and assessed the methylation status of the DNA by pyrosequencing candidate loci as well as with HumanMethylation450 arrays. We found that methylation levels of repetitive elements LINE-1 and SAT-α showed minimal variability throughout the colon in contrast to other loci. Promoter methylation of EVL was highest in the rectum and progressively lower in the proximal segments, whereas ESR1 methylation was higher in older individuals. Genome-wide methylation analysis of normal DNA revealed 8388, 82, and 93 differentially methylated loci that distinguished right from left colon, males from females, and older vs. younger individuals, respectively. Although variability in methylation between biopsies and among different colon segments was minimal for repetitive elements, analyses of specific cancer-related genes as well as a genome-wide methylation analysis demonstrated differential methylation based on colon location, individual age, and gender. These studies advance our knowledge regarding the variation of DNA methylation in the normal colon, a prerequisite for future studies aimed at understanding methylation differences indicative of a colon field effect. 相似文献
939.
940.