全文获取类型
收费全文 | 894篇 |
免费 | 76篇 |
国内免费 | 90篇 |
出版年
2024年 | 2篇 |
2023年 | 14篇 |
2022年 | 15篇 |
2021年 | 40篇 |
2020年 | 27篇 |
2019年 | 34篇 |
2018年 | 36篇 |
2017年 | 31篇 |
2016年 | 38篇 |
2015年 | 69篇 |
2014年 | 63篇 |
2013年 | 63篇 |
2012年 | 78篇 |
2011年 | 59篇 |
2010年 | 45篇 |
2009年 | 36篇 |
2008年 | 59篇 |
2007年 | 38篇 |
2006年 | 32篇 |
2005年 | 42篇 |
2004年 | 27篇 |
2003年 | 35篇 |
2002年 | 25篇 |
2001年 | 22篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 7篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 8篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1987年 | 5篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 4篇 |
1968年 | 2篇 |
排序方式: 共有1060条查询结果,搜索用时 31 毫秒
31.
32.
CYP2J2 and its metabolites (epoxyeicosatrienoic acids) attenuate cardiac hypertrophy by activating AMPKα2 and enhancing nuclear translocation of Akt1
下载免费PDF全文
![点击此处可从《Aging cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cytochrome P450 epoyxgenase 2J2 and epoxyeicosatrienoic acids (EETs) are known to protect against cardiac hypertrophy and heart failure, which involve the activation of 5′‐AMP‐activated protein kinase (AMPK) and Akt. Although the functional roles of AMPK and Akt are well established, the significance of cross talk between them in the development of cardiac hypertrophy and antihypertrophy of CYP2J2 and EETs remains unclear. We investigated whether CYP2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1. Moreover, we tested whether EETs enhanced cross talk between AMPKα2 and phosphorylated Akt1 (p‐Akt1), and stimulated nuclear translocation of p‐Akt1, to exert their antihypertrophic effects. AMPKα2?/? mice that overexpressed CYP2J2 in heart were treated with Ang II for 2 weeks. Interestingly, overexpression of CYP2J2 suppressed cardiac hypertrophy and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild‐type mice but not AMPKα2?/? mice. The CYP2J2 metabolites, 11,12‐EET, activated AMPKα2 to induce nuclear translocation of p‐Akt1 selectively, which increased the production of ANP and therefore inhibited the development of cardiac hypertrophy. Furthermore, by co‐immunoprecipitation analysis, we found that AMPKα2β2γ1 and p‐Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain. This interaction was enhanced by 11,12‐EET. Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hypertrophy and suggest that overexpression of CYP2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure. 相似文献
33.
34.
Zhen‐Guo Yan Li‐Hang Xie Ning Wang Dao‐Yang Sun Zhang‐Zhen Bai Li‐Xin Niu Yan‐Long Zhang Xiao‐Tong Ji 《化学与生物多样性》2019,16(3)
Herbaceous peony has been widely cultivated in China due to its substantial ornamental and medicinal value. In the present study, the phenotypic characteristics, total fatty acid (FA) content, and nine FA compositions of herbaceous peony seeds from 14 populations belonging to six species and one subspecies were determined by normal test and gas chromatography/mass spectrometry (GC/MS). The results showed that the phenotypic characteristics of seeds varied dramatically among species. The concentrations of five major FAs in seed oils were as follows: linoleic acid (173.95–236.51 μg/mg), linolenic acid (227.82–302.71 μg/mg), oleic acid (135.32–208.81 μg/mg), stearic acid (6.52–11.7 μg/mg), and palmitic acid (30.67–47.64 μg/mg). Correlation analysis demonstrated that oleic acid had the highest partial correlation coefficient with total FAs and might be applied to develop a model of phenotypic characteristics. FAs were significantly influenced by the following environmental factors: latitude, elevation, and annual average temperature. Based on the FA levels in the seed oils, clustering analysis divided 14 populations into two clusters. It was found that the average contents of oleic acid, linoleic acid, and total FAs in cluster I (147.16 μg/mg, 200.31 μg/mg, and 671.24 μg/mg, respectively) were significantly lower than those in cluster II (196.65 μg/mg, 220.16 μg/mg, and 741.78 μg/mg, respectively). Cluster I was perfectly consistent with subsect. Foliolatae, while cluster II was in good agreement with subsect. Dissectifoliae. Therefore, the FA composition of wild herbaceous peony seed oil might be used as a chemotaxonomic marker. 相似文献
35.
36.
Duc Khanh Le Quang Khai Le Thi Thuy Hang Tran Duc Viet Nguyen Thi Hang Dao Thi Thuy Nguyen Xuan Lam Truong Quang Cuong Nguyen Huy Phong Pham Thi Thu Thuy Phan Gajendra Babu Baktavachalam 《Journal of Asia》2019,22(2):493-498
Susceptibility of Asian corn borer (ACB), Ostrinia furnacalis (Guenée) to Bacillus thuringiensis (Bt) Cry1Ab protein was studied between 2015 and 2016 with 11 ACB populations, collected from various geographical regions in Vietnam. A concentration range of Cry1Ab from 0.20 to 26.10 ng/cm2 of diet was evaluated against F1 ACB neonates using diet surface-overlay bioassays. Mortality data was recorded daily until seven days after infestation. Growth inhibition was recorded at the end of seven days. The median lethal concentration (LC50) varied ≈3-fold among the different populations, ranging from 0.58 to 1.83 ng/cm2 of diet with an overall mean of 0.86 ng/cm2 of diet. Even the lowest concentration of 0.20 ng/cm2 caused 73.53% growth inhibition. >90% growth inhibition was achieved at 0.82 ng/cm2 or higher concentrations. The results reflect natural variation in Bt susceptibility among ACB populations rather than variation caused by prior exposure to selection pressures. LC99 value (17.26 ng/cm2) was generated by pooling mortality data across different populations. The upper fiducial limit of LC99 (24.38 ng/cm2) could be a potential diagnostic dose for future resistance monitoring programs. The findings from this study suggest that ACB populations in Vietnam are highly susceptible to Cry1Ab protein. This is the first report of Cry1Ab susceptibility of different ACB populations in Vietnam and will serve as a baseline for future resistance monitoring work. 相似文献
37.
Jun-Li Yang Trong Tuan Dao Tran Thi Hien Ya-Min Zhao Yan-Ping Shi 《Bioorganic & medicinal chemistry letters》2019,29(10):1162-1167
The rhizomes of Homalomena occulta are called Qian-nian-jian in Traditional Chinese Medicine (TCM), which is widely consumed in China owing to its health benefits for the treatment of rheumatoid arthritis and for strengthening tendons and bones. A phytochemical investigation on this famous TCM yielded 19 sesquiterpenoids (1–19) with various carbocyclic skeletons including isodaucane (2, 8, and 9), guaiane (3), eudesmane (4 and 10–15), oppositane (5, 16, and 17), and aromadendrane (18 and 19) types. The structures of new compounds, Homalomenins A-E (1–5), were determined by diverse spectroscopic data. Compound 1 possessed a rare sesquiterpenoid skeleton and compound 5 represented the first example of 1,4-oxa-oppositane sesquiterpenoid. These isolates were evaluated for their inhibitory effects on COX-2 mRNA, COX-2 protein expression, and prostaglandin E2 (PGE2) production in Raw264.7 cells, which demonstrated that compounds 5, 18, 19 showed potent anti-inflammatory activity by suppressing LPS-induced COX-2 expression and PGE2 production in a dose-dependent manner. 相似文献
38.
39.
Yao J Kim TW Qin J Jiang Z Qian Y Xiao H Lu Y Qian W Gulen MF Sizemore N DiDonato J Sato S Akira S Su B Li X 《The Journal of biological chemistry》2007,282(9):6075-6089
Interleukin-1 (IL-1) receptor-associated kinase (IRAK) is phosphorylated after it is recruited to the receptor, subsequently ubiquitinated, and eventually degraded upon IL-1 stimulation. Although a point mutation changing lysine 134 to arginine (K134R) in IRAK abolished IL-1-induced IRAK ubiquitination and degradation, mutations of serines and threonines adjacent to lysine 134 to alanines ((S/T)A (131-144)) reduced IL-1-induced IRAK phosphorylation and abolished IRAK ubiquitination. Through the study of these IRAK modification mutants, we uncovered two parallel IL-1-mediated signaling pathways for NFkappaB activation, TAK1-dependent and MEKK3-dependent, respectively. These two pathways bifurcate at the level of IRAK modification. The TAK1-dependent pathway leads to IKKalpha/beta phosphorylation and IKKbeta activation, resulting in classical NFkappaB activation through IkappaBalpha phosphorylation and degradation. The TAK1-independent MEKK3-dependent pathway involves IKKgamma phosphorylation and IKKalpha activation, resulting in NFkappaB activation through IkappaBalpha phosphorylation and subsequent dissociation from NFkappaB but without IkappaBalpha degradation. These results provide significant insight to our further understanding of NFkappaB activation pathways. 相似文献
40.
Shuyu Xin Lingzhi Liu Yanling Li Jing Yang Lielian Zuo Pengfei Cao Qijia Yan Shen Li Li Yang Taimei Cui Jianhong Lu 《中国病毒学》2022,37(6):913-921
The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma (NPC), which is prevalent in southern China and closely related to Epstein-Barr virus (EBV) infection. How these master pathways are persistently activated in EBV-associated NPC remains to be investigated. Here we demonstrated that EBV-encoded latent membrane protein 1 (LMP1) promoted cyclophilin A (CYPA) expression through the activation of NF-κB. The depletion of CYPA suppressed cell proliferation and facilitated apoptosis. CYPA was able to bind to AKT1, thus activating AKT/mTOR/NF-κB signaling cascade. Moreover, the use of mTOR inhibitor, rapamycin, subverted the activation of the positive feedback loop, NF-κB/CYPA/AKT/mTOR. It is reasonable that LMP1 expression derived from initial viral infection is enough to assure the constant potentiation of AKT/mTOR and NF-κB signalings. This may partly explain the fact that EBV serves as a tumor-promoting factor with minimal expression of the viral oncoprotein LMP1 in malignancies. Our findings provide new insight into the understanding of causative role of EBV in tumorigenicity during latent infection. 相似文献