全文获取类型
收费全文 | 1975篇 |
免费 | 101篇 |
专业分类
2076篇 |
出版年
2024年 | 1篇 |
2023年 | 9篇 |
2022年 | 16篇 |
2021年 | 53篇 |
2020年 | 28篇 |
2019年 | 39篇 |
2018年 | 47篇 |
2017年 | 45篇 |
2016年 | 69篇 |
2015年 | 90篇 |
2014年 | 110篇 |
2013年 | 121篇 |
2012年 | 182篇 |
2011年 | 160篇 |
2010年 | 110篇 |
2009年 | 99篇 |
2008年 | 152篇 |
2007年 | 108篇 |
2006年 | 108篇 |
2005年 | 117篇 |
2004年 | 113篇 |
2003年 | 95篇 |
2002年 | 78篇 |
2001年 | 7篇 |
2000年 | 6篇 |
1999年 | 21篇 |
1998年 | 12篇 |
1997年 | 12篇 |
1996年 | 6篇 |
1995年 | 12篇 |
1994年 | 5篇 |
1993年 | 8篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有2076条查询结果,搜索用时 0 毫秒
51.
52.
53.
Yasuo Oowatari Tetsuro Ogawa Takuya Katsube Kiyohisa Iinuma Hisae Yoshitomi Ming Gao 《Bioscience, biotechnology, and biochemistry》2016,80(8):1594-1601
Hypertrophy of adipocytes in obese adipose tissues causes metabolic abnormality by adipocytokine dysregulation, which promotes type 2 diabetes mellitus, hypertension, and dyslipidemia. We investigated the effects of wasabi (Wasabia japonica Matsum) leaf extracts on metabolic abnormalities in SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP/ZF), which are a model of metabolic syndrome. Male SHRSP/ZF rats aged 7 weeks were divided into two groups: control and wasabi leaf extract (WLE) groups, which received water or oral treatment with 4 g/kg/day WLE for 6 weeks. WLE improved the body weight gain and high blood pressure in SHRSP/ZF rats, and the plasma triglyceride levels were significantly lower in the WLE group. Adipocyte hypertrophy was markedly prevented in adipose tissue. The expression of PPARγ and subsequent downstream genes was suppressed in the WLE group adipose tissues. Our data suggest that WLE inhibits adipose hypertrophy by suppressing PPARγ expression in adipose tissue and stimulating the AMPK activity by increased adiponectin. 相似文献
54.
Takuya Tomita Andreas Matouschek 《Protein science : a publication of the Protein Society》2019,28(7):1222-1232
Proteins in the cell have to be eliminated once their function is no longer desired or they become damaged. Most regulated protein degradation is achieved by a large enzymatic complex called the proteasome. Many proteasome substrates are targeted for degradation by the covalent attachment of ubiquitin molecules. Ubiquitinated proteins can be bound by the proteasome, but for proteolysis to occur the proteasome needs to find a disordered tail somewhere in the target at which it initiates degradation. The initiation step contributes to the specificity of proteasomal degradation. Here, we review how the proteasome selects initiation sites within its substrates and discuss how the initiation step affects physiological processes. 相似文献
55.
Yu Kitadate David J. Jörg Moe Tokue Ayumi Maruyama Rie Ichikawa Soken Tsuchiya Eri Segi-Nishida Toshinori Nakagawa Aya Uchida Chiharu Kimura-Yoshida Seiya Mizuno Fumihiro Sugiyama Takuya Azami Masatsugu Ema Chiyo Noda Satoru Kobayashi Isao Matsuo Yoshiakira Kanai Shosei Yoshida 《Cell Stem Cell》2019,24(1):79-92.e6
56.
Morita Y Araki H Sugimoto T Takeuchi K Yamane T Maeda T Yamamoto Y Nishi K Asano M Shirahama-Noda K Nishimura M Uzu T Hara-Nishimura I Koya D Kashiwagi A Ohkubo I 《FEBS letters》2007,581(7):1417-1424
Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells. 相似文献
57.
Gliclazide inhibits proliferation but stimulates differentiation of white and brown adipocytes 总被引:1,自引:0,他引:1
Nakano N Miyazawa N Sakurai T Kizaki T Kimoto K Takahashi K Ishida H Takahashi M Suzuki K Ohno H 《Journal of biochemistry》2007,142(5):639-645
Gliclazide, a second-generation sulfonylurea, has anti-oxidant properties as well as hypoglycemic activities. In the present study, we investigated whether gliclazide affected proliferation and/or differentiation of HW white and HB2 brown adipocyte cell lines. Gliclazide inhibited proliferation of HW and HB2 cells in the medium containing fetal calf serum or epidermal growth factor (EGF). Gliclazide inhibited phosphorylation of EGF receptor and of extracellular signal-regulated kinase (ERK) 1/2 stimulated by EGF. Gliclazide increased lipid accumulation and peroxisome proliferator-activated receptor gamma (PPARgamma) expression in the early stage of differentiation of adipocytes. A K(ATP) channel activator, diazoxide, did not inhibit the increase of lipid accumulation by gliclazide. Furthermore, gliclazide inhibited the DNA-binding activity of PPARgamma in mature adipocytes. On the other hand, glibenclamide, other sulfonylurea, did not show these effects. These results indicate gliclazide inhibits proliferation and stimulates differentiation of adipocytes via down-regulation of the EGFR signalling. Gliclazide may have preventive and therapeutic effects on obesity, as well as on type 2 diabetes. 相似文献
58.
59.
Naohiro Nishikawa Yoshitake Sakae Takuya Gouda Yuichiro Tsujimura Yuko Okamoto 《Biophysical journal》2019,116(5):781-790
A peptide -, which is a fragment from residue 21 to residue 31 of -microgloblin, is experimentally known to self-assemble and form amyloid fibrils. In order to understand the mechanism of amyloid fibril formations, we applied the replica-exchange molecular dynamics method to the system consisting of three fragments of -. From the analyses on the temperature dependence, we found that there is a clear phase transition temperature in which the peptides aggregate with each other. Moreover, we found by the free energy analyses that there are two major stable states: One of them is like amyloid fibrils and the other is amorphous aggregates. 相似文献
60.
Takeshi Kikko Daisuke Ishizaki Taiga Yodo Shizuo Aino Kunihiko Kuwamura Haruo Okamoto Morihito Nemoto Kazuki Yoneda Nobuyuki Oue Akihisa Sakai Yasuhiro Fujioka Yoshiaki Kai Takuya Sato Kouji Nakayama 《Journal of fish biology》2019,95(2):668-672
Otolith growth increments in wild-caught alizarin complex one (ALC)-marked honmoroko Gnathopogon caerulescens were examined to verify the veracity of the age determination method in cyprinids. ALC-marked G. caerulescens recaptured from their natural environment had lapilli increment counts outside the ALC ring mark that had formed on a daily basis during the juvenile stage. This apparently being the first direct evidence of daily periodicity of otolith increment formation in wild-caught cyprinids. 相似文献