全文获取类型
收费全文 | 774篇 |
免费 | 49篇 |
专业分类
823篇 |
出版年
2023年 | 3篇 |
2022年 | 17篇 |
2021年 | 29篇 |
2020年 | 12篇 |
2019年 | 15篇 |
2018年 | 17篇 |
2017年 | 12篇 |
2016年 | 39篇 |
2015年 | 42篇 |
2014年 | 62篇 |
2013年 | 47篇 |
2012年 | 64篇 |
2011年 | 69篇 |
2010年 | 52篇 |
2009年 | 33篇 |
2008年 | 46篇 |
2007年 | 28篇 |
2006年 | 43篇 |
2005年 | 36篇 |
2004年 | 34篇 |
2003年 | 35篇 |
2002年 | 23篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 11篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1976年 | 2篇 |
排序方式: 共有823条查询结果,搜索用时 0 毫秒
61.
Imai K Inukai K Ikegami Y Awata T Katayama S 《Biochemical and biophysical research communications》2006,351(3):595-601
LKB1 is a 50 kDa serine/threonine kinase that phosphorylates and activates the catalytic subunit of AMPK at its T-loop residue Thr 172. We prepared adenoviruses expressing the constitutive active (wild-type) form (CA) or dominant negative (kinase inactive, D194A mutant) form (DN) of LKB1 and overexpressed these proteins in cultured myotubes (C2C12 cells) and rat hepatoma cells (FAO cells). When analyzed by immunoblotting with the antibody against Thr172-phosphorylated AMPK, the phosphorylation of AMPK was increased (2.5-fold) and decreased (0.4-fold) in cells expressing CA and DN LKB1, respectively, as compared with Lac-Z expressing control cells. Immunoprecipitation experiments, using isoform-specific antibody, revealed these alterations of AMPK phosphorylation to be attributable to altered phosphorylation of AMPK alpha2, but not alpha1 catalytic subunits, strongly suggesting the alpha2 catalytic subunit to be the major substrate for LKB1 in mammalian cells. In addition, adiponectin or AICAR-stimulated AMPK phosphorylation was inhibited by overexpression of DN LKB1, while phenformin-stimulated phosphorylation was unaffected. These results may explain the difference in AMPK activation mechanisms between AMP and phenformin, and also indicate that AMPK phosphorylation by LKB1 is involved in AMP-stimulated AMPK activation. As a downstream target for AMPK, AICAR-induced glucose uptake and ACCbeta phosphorylation were found to be significantly reduced in DN LKB1 expressing C2C12 cells. The expression of key enzymes for gluconeogenesis, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was also dependent on LKB1 activities in FAO cells. These results demonstrate that LKB1 is a crucial regulator of AMPK activation in muscle and liver cells and, therefore, that LKB1 activity is potentially of importance to our understanding of glucose and lipid metabolism. 相似文献
62.
When activated by viral infection, plasmacytoid dendritic cells (pDCs) play a primary role in the immune response through secretion of IFN-α. Lactococcus lactis subsp. lactis JCM5805 (JCM5805) is a strain of lactic acid bacteria (LAB) that activates murine and human pDCs to express type I and type III interferons (IFNs). JCM5805 has also been shown to activate pDCs via a Toll-like receptor 9 (TLR9) dependent pathway. In this study, we investigated the anti-viral effects of oral administration of JCM5805 using a mouse model of murine parainfluenza virus (mPIV1) infection. JCM5805-fed mice showed a drastic improvement in survival rate, prevention of weight loss, and reduction in lung histopathology scores compared to control mice. We further examined the mechanism of anti-viral effects elicited by JCM5805 administration using naive mice. Microscopic observations showed that JCM5805 was incorporated into CD11c+ immune cells in Peyer’s patches (PP) and PP pDCs were significantly activated and the expression levels of IFNs were significantly increased. Interestingly, nevertheless resident pDCs at lung were not activated and expressions levels of IFNs at whole lung tissue were not influenced, the expressions of anti-viral factors induced by IFNs, such as Isg15, Oasl2, and Viperin, at lung were up-regulated in JCM5805-fed mice compared to control mice. Therefore expressed IFNs from intestine might be delivered to lung and IFN stimulated genes might be induced. Furthermore, elevated expressions of type I IFNs from lung lymphocytes were observed in response to mPIV1 ex vivo stimulation in JCM5805-fed mice compared to control. This might be due to increased ratio of pDCs located in lung were significantly increased in JCM5805 group. Taken together, a specific LAB strain might be able to affect anti-viral immunological profile in lung via activation of intestinal pDC leading to enhanced anti-viral phenotype in vivo. 相似文献
63.
Nakano T Inoue I Koyama I Kanazawa K Nakamura K Narisawa S Tanaka K Akita M Masuyama T Seo M Hokari S Katayama S Alpers DH Millán JL Komoda T 《American journal of physiology. Gastrointestinal and liver physiology》2007,292(5):G1439-G1449
Intestinal alkaline phosphatase (IAP) is involved in the process of fat absorption, a conclusion confirmed by an altered lipid transport and a faster body weight gain from 10 to 30 wk in both male and female mice with a homozygous null mutation of the IAP coding gene (Akp3(-/-) mice). This study was aimed to delineate morphologically and quantitatively the accelerated lipid absorption in male Akp3(-/-) mice. Feeding a corn oil bolus produced an earlier peak of triacylglycerol in serum (2 vs. 4 h for Akp3(-/-) and wild-type mice, respectively) and an approximately twofold increase in serum triacylglycerol concentration in Akp3(-/-) mice injected with a lipolysis inhibitor, Triton WR-1339. A corn oil load induced the threefold enlargement of the Golgi vacuoles in male wild-type mice but not in Akp3(-/-) mice, indicating that absorbed lipids rarely reached the Golgi complex and that the transcytosis of lipid droplets does not follow the normal pathway in male Akp3(-/-) mice. Force feeding an exaggerated fat intake by a 30% fat chow for 10 wk induced obesity in both male Akp3(-/-) and wild-type mice, and therefore no phenotypic difference was observed between the two. On the other hand, the forced high-fat chow induced an 18% greater body weight gain, hepatic steatosis, and visceral fat accumulation in female Akp3(-/-) mice but not in female wild-type controls. These results provide further evidence that IAP is involved in the regulation of the lipid absorption process and that its absence leads to progressive metabolic abnormalities in certain fat-forced conditions. 相似文献
64.
65.
Cloning, Functional Characterization, and Mode of Action of a Novel Insecticidal Pore-Forming Toxin, Sphaericolysin, Produced by Bacillus sphaericus 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hisashi Nishiwaki Kenta Nakashima Chiharu Ishida Tadayuki Kawamura Kazuhiko Matsuda 《Applied microbiology》2007,73(10):3404-3411
An insecticidal protein produced by Bacillus sphaericus A3-2 was purified to elucidate its structure and mode of action. The active principle purified from the culture broth of A3-2 was a protein with a molecular mass of 53 kDa that rapidly intoxicated German cockroaches (Blattela germanica) at a dose of about 100 ng when injected. The insecticidal protein sphaericolysin possessed the undecapeptide motif of cholesterol-dependent cytolysins and had a unique N-terminal sequence. The recombinant protein expressed in Escherichia coli was equally as potent as the native protein. Sphaericolysin-induced hemolysis resulted from the protein's pore-forming action. This activity as well as the insecticidal activity was markedly reduced by a Y159A mutation. Also, coapplication of sphaericolysin with cholesterol abolished the insecticidal action, suggesting that cholesterol binding plays an important role in insecticidal activity. Sphaericolysin-lysed neurons dissociated from the thoracic ganglia of the German cockroaches. In addition, sphaericolysin's activity in ganglia was suppressed by the Y159A mutation. The sphaericolysin-induced damage to the cockroach ganglia was greater than the damage to the ganglia of common cutworms (Spodoptera litura), which accounts, at least in part, for the higher sensitivity to sphaericolysin displayed by the cockroaches than that displayed by cutworms. 相似文献
66.
67.
Teruyoshi Nagamitsu Tanaka Kenta Naoki Inari Haruka Horita Koichi Goka Tsutom Hiura 《Journal of Insect Conservation》2007,11(2):123-130
To assess the impact of Bombus terrestris invasion on the foraging efficiency of native Japanese bumblebees, consumption and acquisition of floral resources during
foraging on flowers of native Japanese plant species were investigated using enclosures with three treatments: one with only
B. terrestris (exotic), one with both B. terrestris and native Japanese bumblebee species (mixed), and one with only Japanese species (native), but with the bumblebee density
held constant. Changes in the body mass of queens and the nest mass of colonies for two days did not significantly differ
among four combinations of the species and treatment, B. terrestris in the exotic and mixed treatments and Japanese species in the mixed and native treatments. Thus, it is not clear that B. terrestris has higher foraging efficiency than native species and that B. terrestris individuals more negatively affect the foraging efficiency of native species than individuals of the native species themselves.
The nectar standing crop of Cirsium kamtschaticum was smaller in the exotic treatment than in the mixed and native treatments. However, this may have been an artifact of differences
in the numbers of flowers in the various treatments.
T. Nagamitsu and T. Kenta contributed equally to this work 相似文献
68.
Masuya H Sezutsu H Sakuraba Y Sagai T Hosoya M Kaneda H Miura I Kobayashi K Sumiyama K Shimizu A Nagano J Yokoyama H Kaneko S Sakurai N Okagaki Y Noda T Wakana S Gondo Y Shiroishi T 《Genomics》2007,89(2):207-214
Mammal-fish-conserved-sequence 1 (MFCS1) is a highly conserved sequence that acts as a limb-specific cis-acting regulator of Sonic hedgehog (Shh) expression, residing 1 Mb away from the Shh coding sequence in mouse. Using gene-driven screening of an ENU-mutagenized mouse archive, we obtained mice with three new point mutations in MFCS1: M101116, M101117, and M101192. Phenotype analysis revealed that M101116 mice exhibit preaxial polydactyly and ectopic Shh expression at the anterior margin of the limb buds like a previously identified mutant, M100081. In contrast, M101117 and M101192 show no marked abnormalities in limb morphology. Furthermore, transgenic analysis revealed that the M101116 and M100081 sequences drive ectopic reporter gene expression at the anterior margin of the limb bud, in addition to the normal posterior expression. Such ectopic expression was not observed in the embryos carrying a reporter transgene driven by M101117. These results suggest that M101116 and M100081 affect the negative regulatory activity of MFCS1, which suppresses anterior Shh expression in developing limb buds. Thus, this study shows that gene-driven screening for ENU-induced mutations is an effective approach for exploring the function of conserved, noncoding sequences and potential cis-regulatory elements. 相似文献
69.
70.
Ujifuku Kenta Fujimoto Takashi Sato Kei Morofuji Yoichi Muto Hideki Masumoto Hiroshi Nakagawa Shinsuke Niwa Masami Matsuo Takayuki 《Cellular and molecular neurobiology》2022,42(4):997-1004
Cellular and Molecular Neurobiology - Metastatic brain tumors have poor prognoses and pose unmet clinical problems for the patients. The blood–brain barrier (BBB) implication is supposed to... 相似文献