全文获取类型
收费全文 | 67244篇 |
免费 | 6254篇 |
国内免费 | 2607篇 |
专业分类
耳鼻咽喉 | 741篇 |
儿科学 | 1610篇 |
妇产科学 | 1238篇 |
基础医学 | 7073篇 |
口腔科学 | 1413篇 |
临床医学 | 6186篇 |
内科学 | 6227篇 |
皮肤病学 | 1251篇 |
神经病学 | 2375篇 |
特种医学 | 3536篇 |
外国民族医学 | 62篇 |
外科学 | 8333篇 |
综合类 | 11466篇 |
现状与发展 | 21篇 |
预防医学 | 1807篇 |
眼科学 | 746篇 |
药学 | 4583篇 |
47篇 | |
中国医学 | 2001篇 |
肿瘤学 | 15389篇 |
出版年
2024年 | 66篇 |
2023年 | 962篇 |
2022年 | 1489篇 |
2021年 | 2688篇 |
2020年 | 2360篇 |
2019年 | 2120篇 |
2018年 | 1977篇 |
2017年 | 2249篇 |
2016年 | 2531篇 |
2015年 | 2727篇 |
2014年 | 4136篇 |
2013年 | 4261篇 |
2012年 | 3744篇 |
2011年 | 4184篇 |
2010年 | 3361篇 |
2009年 | 3372篇 |
2008年 | 3390篇 |
2007年 | 3654篇 |
2006年 | 3301篇 |
2005年 | 2969篇 |
2004年 | 2573篇 |
2003年 | 2202篇 |
2002年 | 2028篇 |
2001年 | 1825篇 |
2000年 | 1501篇 |
1999年 | 1342篇 |
1998年 | 1109篇 |
1997年 | 981篇 |
1996年 | 863篇 |
1995年 | 876篇 |
1994年 | 753篇 |
1993年 | 602篇 |
1992年 | 515篇 |
1991年 | 463篇 |
1990年 | 359篇 |
1989年 | 338篇 |
1988年 | 311篇 |
1987年 | 264篇 |
1986年 | 211篇 |
1985年 | 253篇 |
1984年 | 234篇 |
1983年 | 155篇 |
1982年 | 186篇 |
1981年 | 155篇 |
1980年 | 123篇 |
1979年 | 106篇 |
1978年 | 74篇 |
1977年 | 62篇 |
1976年 | 51篇 |
1975年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 19 毫秒
991.
Hyperpolarized [1,3‐13C2]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer 下载免费PDF全文
Pernille R. Jensen Sonia Colombo Serra Luigi Miragoli Magnus Karlsson Claudia Cabella Luisa Poggi Luca Venturi Fabio Tedoldi Mathilde H. Lerche 《International journal of cancer. Journal international du cancer》2015,136(4):E117-E126
An increased prevalence of liver diseases such as hepatitis C and nonalcoholic fatty liver results in an augmented incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC). HCC is most often found in the cirrhotic liver and it can therefore be challenging to rely on anatomical information alone when diagnosing HCC. Valuable information on specific cellular metabolism can be obtained with high sensitivity thanks to an emerging magnetic resonance (MR) technique that uses 13C labeled hyperpolarized molecules. Our interest was to explore potential new high contrast metabolic markers of HCC using hyperpolarized 13C‐MR. This work led to the identification of a class of substrates, low molecular weight ethyl‐esters, which showed high specificity for carboxyl esterases and proved in many cases to possess good properties for signal enhancement. In particular, hyperpolarized [1,3‐13C2]ethyl acetoacetate (EAA) was shown to provide a metabolic fingerprint of HCC. Using this substrate a liver cancer implanted in rats was diagnosed as a consequence of an ~4 times higher metabolic substrate‐to‐product ratio than in the surrounding healthy tissue, (p = 0.009). Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized 13C‐MR marker. This could be appreciated by the signal‐to‐noise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state‐of‐the‐art hyperpolarized substrate, [1‐13C]pyruvate. Also, the contrast‐to‐noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1‐13C]pyruvate. 相似文献
992.
The clinical utility of serum anti‐Müllerian hormone in the follow‐up of ovarian adult‐type granulosa cell tumors—A comparative study with inhibin B 下载免费PDF全文
Anniina Färkkilä Sanna Koskela Saara Bryk Henrik Alfthan Ralf Bützow Arto Leminen Ulla Puistola Juha S. Tapanainen Markku Heikinheimo Mikko Anttonen Leila Unkila‐Kallio 《International journal of cancer. Journal international du cancer》2015,137(7):1661-1671
Ovarian adult‐type granulosa cell tumors (AGCTs) require prolonged follow‐up, but evidence regarding the optimal follow‐up marker is lacking. The objective of our study was to validate the clinical usefulness of serum anti‐Müllerian hormone (AMH) and the current marker inhibin B as single and combined markers of AGCTs. We conducted a longitudinal, partially prospective cohort study of 123 premenopausal and postmenopausal AGCT patients with a median follow‐up time of 10.5 years (range 0.3–50.0 years). Serum AMH and inhibin B levels were measured from 560 pretreatment and follow‐up serum samples by using immunoenzymometric assays. We found that serum AMH and inhibin B levels were significantly elevated in patients with primary or recurrent AGCTs. The levels of both markers positively correlated to tumor size (p < 0.05). AMH and inhibin B performed similarly in receiving operator characteristic analyses; area under the curve (AUC) values were 0.92 [95% confidence interval (CI) 0.88–0.95] for AMH, and 0.94 (95% CI 0.90–0.96) for inhibin B. AMH was highly sensitive (92%) and specific (81%) in detecting a macroscopic AGCT. However, in AUC comparison analyses, the combination of the markers was superior to inhibin B alone. In conclusion, serum AMH is a sensitive and specific marker of AGCT, and either AMH or inhibin B can be monitored during follow‐up. However, combining AMH and inhibin B in AGCT patient follow‐up improves the detection of recurrent disease. 相似文献
993.
Negative modulation of the epigenetic regulator,UHRF1, by thyroid hormone receptors suppresses liver cancer cell growth 下载免费PDF全文
Sheng‐Ming Wu Wan‐Li Cheng Chia‐Jung Liao Hsiang‐Cheng Chi Yang‐Hsiang Lin Yi‐Hsin Tseng Chung‐Ying Tsai Ching‐Ying Chen Syuan‐Ling Lin Wei‐Jan Chen Yung‐Hsin Yeh Chi‐Ying F. Huang Ming‐Huang Chen Yi‐Chen Yeh Kwang‐Huei Lin 《International journal of cancer. Journal international du cancer》2015,137(1):37-49
The thyroid hormone, 3,3′,5‐triiodo‐l ‐thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation, metabolism and regulation of cell proliferation. Thyroid hormone (T3) and its receptor (TR) are involved in metabolism and growth. In addition to their developmental and metabolic functions, TRs play a tumor suppressor role, and therefore, their aberrant expression can lead to tumor transformation. Aberrant epigenetic silencing of tumor suppressor genes promotes cancer progression. The epigenetic regulator, Ubiquitin‐like with PHD and ring finger domains 1 (UHRF1), is overexpressed in various cancers. In our study, we demonstrated that T3 negatively regulates UHRF1 expression, both in vitro and in vivo. Our results further indicate that UHRF1 regulation by T3 is indirect and mediated by Sp1. Sp1‐binding elements of UHRF1 were identified at positions ?664/?505 of the promoter region using the luciferase and chromatin immunoprecipitation assays. Notably, UHRF1 and Sp1 levels were elevated in subgroups of hepatocellular carcinoma patients and inversely correlated with TRα1 expression. Knockdown of UHRF1 expression should therefore provide a means to inhibit hepatoma cell proliferation. Expression of UHRF1 was downregulated by TRs, in turn, relieving silencing of the UHRF1 target gene, p21. Based on the collective findings, we propose that T3/TR signaling induces hepatoma cell growth inhibition via UHRF1 repression. 相似文献
994.
Trends and predictors of resection of the primary tumor for patients with stage IV colorectal cancer 下载免费PDF全文
995.
996.
997.
Silibinin prevents prostate cancer cell‐mediated differentiation of naïve fibroblasts into cancer‐associated fibroblast phenotype by targeting TGF β2 下载免费PDF全文
998.
999.
Wnt‐3a‐activated human fibroblasts promote human keratinocyte proliferation and matrix destruction 下载免费PDF全文
Hans‐Jürgen Stark Hermann Stammer Silke Prätzel‐Wunder Jackie R Bickenbach Petra Boukamp 《International journal of cancer. Journal international du cancer》2015,136(12):2786-2798
Aberrant Wnt regulation, detectable by nuclear translocation of beta‐catenin, is a hallmark of many cancers including skin squamous cell carcinomas (SCCs). By analyzing primary human skin SCCs, we demonstrate that nuclear beta‐catenin is not restricted to SCC cells but also detected in stromal fibroblasts, suggesting an important role for aberrant Wnt regulation also in the tumor microenvironment. When human keratinocytes and fibroblasts were treated with Wnt‐3a, fibroblasts proved to be more responsive. Accordingly, Wnt‐3a did not alter HaCaT cell functions in a cell‐autonomous manner. However, when organotypic cultures (OTCs) were treated with Wnt‐3a, HaCaT keratinocytes responded with increased proliferation. As nuclear beta‐catenin was induced only in the fibroblasts, this argued for a Wnt‐dependent, paracrine keratinocyte stimulation. Global gene expression analysis of Wnt‐3a‐stimulated fibroblasts identified genes encoding interleukin‐8 (IL‐8) and C‐C motif chemokine 2 (CCL‐2) as well as matrix metalloproteinase‐1 (MMP‐1) as Wnt‐3a targets. In agreement, we show that IL‐8 and CCL‐2 were secreted in high amounts by Wnt‐3a‐stimulated fibroblasts also in OTCs. The functional role of IL‐8 and CCL‐2 as keratinocyte growth regulators was confirmed by directly stimulating HaCaT cell proliferation in conventional cultures. Most important, neutralizing antibodies against IL‐8 and CCL‐2 abolished the Wnt‐dependent HaCaT cell hyperproliferation in OTCs. Additionally, MMP‐1 was expressed in high amounts in Wnt‐3a‐stimulated OTCs and degraded the stromal matrix. Thus, our data show that Wnt‐3a stimulates fibroblasts to secrete both keratinocyte proliferation‐inducing cytokines and stroma‐degrading metalloproteinases, thereby providing evidence for a novel Wnt deregulation in the tumor‐stroma directly contributing to skin cancer progression. 相似文献
1000.
Jiao Peng Julia Y. Tsang Derek H. Ho Ruizhong Zhang Haitao Xiao Daxu Li Jiang Zhu Fenghua Wang Zhaoxiang Bian Vincent C. Lui Aimin Xu Paul K. Tam Jonathan R. Lamb Huimin Xia Yan Chen 《International journal of cancer. Journal international du cancer》2015,137(4):848-858
The plasticity of macrophages with selective functional phenotypes partially arises in respective to their microenvironment. Tumor‐associated macrophages (TAMs) may promote disease progression with tumor specific manner. Here we report that in pediatric malignant soft‐tissue tumors, the presence of TAMs and expression of adiponectin (APN) are heterogeneous. Both APN and TAMs had high expression in rhabdomyosarcoma, especially in the malignant subtype, alveolar rhabdomyosarcoma. To investigate the mode of action of APN on TAM activation, a murine MN/MCA1 sarcoma model was used. The Results revealed that exogenous APN had no effect on MN/MCA1 proliferation but tumor size was markedly reduced in apn?/? mice versus WT controls. The accumulation of TAMs in apn?/? mice was also reduced which correlated to downregulated serum levels of MCP‐1. Likewise, TAMs in apn?/? mice exhibited a M1‐like phenotype, characterized by increase in MHC IIhigh population and M1 phenotypic markers, such as iNOS gene and serum TNF‐α accompanied by a decrease in M2 markers, namely YM1 gene and serum IL‐10. In addition, APN deficiency increased the number of CD4+ T cells, CD8+ T cells and NK cells in tumors and reduced tumor metastasis. The altered phenotype of TAMs in apn?/? mice was associated with a marked decrease in phospho‐p38 and treatment with a p38 MAPK inhibitor significantly reduced tumor size and increased MHC II expression on TAMs in WT mice, implying p38 MAPK signaling pathway may contribute to APN‐mediated TAM polarization. Collectively, our findings suggest that APN may have a potential role in regulating soft tissue sarcoma growth. 相似文献