全文获取类型
收费全文 | 587篇 |
免费 | 39篇 |
国内免费 | 16篇 |
出版年
2024年 | 1篇 |
2023年 | 14篇 |
2022年 | 21篇 |
2021年 | 34篇 |
2020年 | 38篇 |
2019年 | 57篇 |
2018年 | 31篇 |
2017年 | 15篇 |
2016年 | 16篇 |
2015年 | 34篇 |
2014年 | 34篇 |
2013年 | 46篇 |
2012年 | 24篇 |
2011年 | 19篇 |
2010年 | 22篇 |
2009年 | 14篇 |
2008年 | 30篇 |
2007年 | 28篇 |
2006年 | 22篇 |
2005年 | 15篇 |
2004年 | 26篇 |
2003年 | 13篇 |
2002年 | 14篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 2篇 |
排序方式: 共有642条查询结果,搜索用时 31 毫秒
71.
72.
成纤维细胞生长因子受体(FGFR)介导的SNT1(亦称为FRS2)底物磷酸化具有宿主细胞以及受体特异性。为探明这种宿主细胞特异性的决定因素,我们构建了1个FGFR2Ⅲb/R1嵌合受体。该嵌合受体具有1个FGFR2Ⅲb的胞外片段及1个FGFR1蛋白质酪氨酸激酶片断。当表达在3T3细胞(内源性受体为FGFR1并能强烈响应FGFR1的信号)以及DTE-R1/100细胞时,该嵌合受体能即刻诱导SNT1磷酸化。DTE-R1/100细胞为经长期培养的带有外源性FGFR1的非恶性前列腺肿瘤上皮细胞(DTE)并已获得未转化DTE细胞所不具备的FGFR1信号响应性。与此相反,当表达在非转化DTE细胞或未经长期培养的FGFR1转化细胞(DTE-R1)时,FGFR2Ⅲb/R1嵌合受体则无法诱导SNT1磷酸化。我们曾报导DTE细胞对FGFR1介导的SNT1磷酸化活力及其刺激细胞生长信号的响应性是一种获得性的性质,这种性质的获得与细胞恶化是紧密联系在一起的。在此我们进一步证明FGFR介导的SNT1磷酸化具有宿主细胞特异性。这些结果表明细胞内围绕着激酶的微环境而不是细胞外环境决定了SNT1是否可为FGFR1所磷酸化。而且,长期受外源性FGFR1刺激诱发DTE细胞内微环境的变化,从而使表达在DTE细胞里的FGFR1激酶可强烈地磷酸化SNT1。 相似文献
73.
74.
Lizhi Lin Jialiang Wen Bangyi Lin Adheesh Bhandari Danni Zheng Lingguo Kong Yinghao Wang Ouchen Wang Yizuo Chen 《Journal of cellular and molecular medicine》2020,24(23):14059
The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up‐regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf‐like PTC patients with higher IMUP expression had shorter disease‐free survival. The biological function of IMUP in PTC cell lines (KTC‐1 and TPC‐1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis‐related molecules were identified by real‐time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down‐regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC. 相似文献
75.
AHNAK controls 53BP1-mediated p53 response by restraining 53BP1 oligomerization and phase separation
Indrajeet Ghodke Michaela Remisova Audrey Furst Sinan Kilic Bernardo Reina-San-Martin Anna R. Poetsch Matthias Altmeyer Evi Soutoglou 《Molecular cell》2021,81(12):2596-2610.e7
- Download : Download high-res image (200KB)
- Download : Download full-size image
76.
In the last 10 years, studies of energetic metabolism in different tumors clearly indicate that the definition of Warburg effect, i.e. the glycolytic shift cells undergo upon transformation, ought to be revisited considering the metabolic plasticity of cancer cells. In fact, recent findings show that the shift from glycolysis to re-established oxidative metabolism is required for certain steps of tumor progression, suggesting that mitochondrial function and, in particular, respiratory complex I are crucial for metabolic and hypoxic adaptation. Based on these evidences, complex I can be considered a lethality target for potential anticancer strategies. In conclusion, in this mini review we summarize and discuss why it is not paradoxical to develop pharmacological and genome editing approaches to target complex I as novel adjuvant therapies for cancer treatment.This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. 相似文献
77.
《Biomarkers》2013,18(2):181-191
Objectives: To identify biomarkers for cancer in asbestosis patients.Methods: SELDI-TOF and CART were used to identify serum biomarker profiles in 35 asbestosis patients who subsequently developed cancer and 35 did not develop cancer.Results: Three polypeptide peaks (5707.01, 6598.10, and 20,780.70?Da) could predict the development of cancer with 87% sensitivity and 70% specificity. The first two peaks were identified as KIF18A and KIF5A, respectively, and are part of the Kinesin Superfamily of proteins.Conclusions: We identified two Kinesin proteins that can be potentially used as blood biomarkers to identify asbestosis patients at risk of developing lung cancer. 相似文献
78.
Mohd M. Khan Orna Ernst Jing Sun Iain D.C. Fraser Robert K. Ernst David R. Goodlett Aleksandra Nita-Lazar 《Journal of molecular biology》2018,430(17):2641-2660
One cause of sepsis is systemic maladaptive immune response of the host to bacteria and specifically, to Gram-negative bacterial outer-membrane glycolipid lipopolysaccharide (LPS). On the host myeloid cell surface, proinflammatory LPS activates the innate immune system via Toll-like receptor-4/myeloid differentiation factor-2 complex. Intracellularly, LPS is also sensed by the noncanonical inflammasome through caspase-11 in mice and 4/5 in humans. The minimal functional determinant for innate immune activation is the membrane anchor of LPS called lipid A. Even subtle modifications to the lipid A scaffold can enable, diminish, or abolish immune activation. Bacteria are known to modify their LPS structure during environmental stress and infection of hosts to alter cellular immune phenotypes. In this review, we describe how mass spectrometry-based structural analysis of endotoxin helped uncover major determinations of molecular pathogenesis. Through characterization of LPS modifications, we now better understand resistance to antibiotics and cationic antimicrobial peptides, as well as how the environment impacts overall endotoxin structure. In addition, mass spectrometry-based systems immunoproteomics approaches can assist in elucidating the immune response against LPS. Many regulatory proteins have been characterized through proteomics and global/targeted analysis of protein modifications, enabling the discovery and characterization of novel endotoxin-mediated protein translational modifications. 相似文献
79.
80.
Evolutionary biogeography of the terrestrial biota of the Marquesas Islands,one of the world's remotest archipelagos
下载免费PDF全文
![点击此处可从《Journal of Biogeography》网站下载免费的PDF全文](/ch/ext_images/free.gif)
David H. Hembry 《Journal of Biogeography》2018,45(8):1713-1726