全文获取类型
收费全文 | 307篇 |
免费 | 13篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2016年 | 6篇 |
2015年 | 10篇 |
2014年 | 8篇 |
2013年 | 25篇 |
2012年 | 23篇 |
2011年 | 18篇 |
2010年 | 8篇 |
2009年 | 20篇 |
2008年 | 28篇 |
2007年 | 23篇 |
2006年 | 21篇 |
2005年 | 23篇 |
2004年 | 19篇 |
2003年 | 19篇 |
2002年 | 16篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有320条查询结果,搜索用时 78 毫秒
131.
Katsura Mochizuki Tomoko Sugita Fumi Yamada Yasunobu Ohgami Syouhei Kato 《Inorganica chimica acta》2010,363(13):3151-3157
New nickel(II) complexes with macrocyclic ligands bearing benzyloxy [(5), (9)], 2-methylbenzyloxy (7), 3-methylbenzyloxy (8), and hydroxy (6) groups on the pyridine ring have been synthesized. Structures of the hydroxy substituted macrocyclic ligand (L-OH·3HCl·H2O), and the benzyloxy substituted ligand (L-OBn·3HCl) and its nickel(II) complex (5), as well as an analogous Ni(II) complex (8), have been revealed by X-ray crystallography. Their catalytic capabilities in the reductive debromination of 1-bromo-4-tert-butylbenzene have been elucidated, which has revealed that the pyridine ring can be a suitable position for the introduction of functional groups while maintaining the catalytic capabilities of the nickel(II) complexes. 相似文献
132.
Sato T Ando Y Susuki S Mikami F Ikemizu S Nakamura M Suhr O Anraku M Kai T Suico MA Shuto T Mizuguchi M Yamagata Y Kai H 《FEBS letters》2006,580(2):491-496
Transthyretin (TTR) amyloid fibril formation, which is triggered by the dissociation of tetrameric TTR, appears to be the causative factor in familial amyloidotic polyneuropathy and senile systemic amyloidosis. Binding of thyroxine (T(4)), a native ligand of TTR, stabilizes the tetramer, but the bioavailability of T(4) for TTR binding is limited due to the preferential binding of T(4) to globulin, the major T(4) carrier in plasma. Here, we show that Cr(3+) increased the T(4)-binding capacity of wild-type (WT) and amyloidogenic V30M-TTR. Moreover, we demonstrate that Cr(3+) and T(4) cooperatively suppressed in vitro fibril formation due to the stabilization of WT-TTR and V30M-TTR. 相似文献
133.
Nakajima H Watanabe N Shibata F Kitamura T Ikeda Y Handa M 《The Journal of biological chemistry》2006,281(20):14494-14502
CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) plays a critical role in terminal myeloid differentiation. Differentiation is an integrated process of cell cycle arrest, morphological change, functional maturation, and apoptosis. However, the molecular networks underlying these events in C/EBPepsilon-induced differentiation remain poorly understood. To reveal these mechanisms, we performed a detailed molecular analysis of C/EBPepsilon-induced differentiation using an inducible form of C/EBPepsilon. The activation of C/EBPepsilon induced growth arrest, morphological differentiation, the expression of CD11b and secondary granule proteins, and apoptosis in myeloid cell lines. Unlike C/EBPalpha, C/EBPepsilon dramatically up-regulated p27 with a concomitant down-regulation of cdk4/6 and cyclin D2/A/E. Moreover, the anti-apoptotic proteins Bcl-2 and Bcl-x were down-regulated, whereas pro-apoptotic protein Bax remained unchanged. Using a variety of mutants, we revealed that these events were all regulated by the N-terminal activation domain of C/EBPepsilon. Interestingly, some of the differentiation processes such as the induction of secondary granule protein genes were clearly inhibited by c-Myc; however, inhibition of apoptosis by Bcl-x did not affect the entire differentiation processes. These data indicate the N terminus of C/EBPepsilon to be solely responsible for most aspects of myeloid differentiation, and these events were differentially affected by c-Myc. 相似文献
134.
Mikami F Lim JH Ishinaga H Ha UH Gu H Koga T Jono H Kai H Li JD 《The Journal of biological chemistry》2006,281(31):22397-22408
The transforming growth factor beta (TGF-beta) pathway represents an important signaling pathway involved in the regulation of diverse biological processes, including cell proliferation, differentiation, and apoptosis. Despite the known role of TGF-betaR-mediated signaling in suppressing immune response, its role in regulating human Toll-like receptors (TLRs), key host defense receptors that recognize invading bacterial pathogens, however, remains unknown. Here, we show for the first time that TGF-betaR-Smad3/4 signaling pathway acts as a positive regulator for TLR2 induction by bacterium nontypeable Hemophilus influenzae (NTHi) in vitro and in vivo. The positive regulation of TLR2 induction by TGF-betaR is mediated via a dual mechanism involving distinct signaling pathways. One mechanism involves functional cooperation between the TGF-betaR-Smad3/4 pathway and NF-kappaB pathway. Another involves MAP kinase phosphatase 1 (MKP-1)-dependent inhibition of p38 MAPK, a known negative regulator for TLR2 induction. Moreover, we showed that TbetaR-mediated signaling is probably activated by NTHi-derived TGF-beta mimicry molecule via an autocrine-independent mechanism. Thus, our study provides new insights into the role of TGF-beta signaling in positively regulating host defense response by tightly controlling the expression level of TLR2 during bacterial infections and may lead to new therapeutic strategies for modulating host defense and inflammatory response. 相似文献
135.
136.
Kamio K Yoshida T Gao C Ishii T Ota F Motegi T Kobayashi S Fujinawa R Ohtsubo K Kitazume S Angata T Azuma A Gemma A Nishimura M Betsuyaku T Kida K Taniguchi N 《Biochemical and biophysical research communications》2012,424(1):112-117
Fut8 (α1,6-Fucosyltransferase) heterozygous knock-out (Fut8(+/-)) mice had an increased influx of inflammatory cells into the lungs, and this was associated with an up-regulation of matrix metalloproteinases, MMP-2 and MMP-9, after treatment with porcine pancreatic elastase (PPE), exhibiting an emphysema-prone phenotype as compared with wild type mice (Fut8(+/+)). The present data as well as our previous data on cigarette-smoke-induced emphysema [8] led us to hypothesize that reduced Fut8 levels leads to COPD with increased inflammatory response in humans and is associated with disease progression. To test this hypothesis, symptomatic current or ex-smokers with stable COPD or at risk outpatients were recruited. We investigated the association between serum Fut8 activity and disease severity, including the extent of emphysema (percentage of low-attenuation area; LAA%), airflow limitation, and the annual rate of decline in forced expiratory volume in 1 s (FEV(1)). Association with the exacerbation of COPD was also evaluated over a 3-year period. Serum Fut8 and MMP-9 activity were measured. Fut8 activity significantly increased with age among the at risk patients. In the case of COPD patients, however, the association was not clearly observed. A faster annual decline of FEV(1) was significantly associated with lower Fut8 activity. Patients with lower Fut8 activity experienced exacerbations more frequently. These data suggest that reduced Fut8 activity is associated with the progression of COPD and serum Fut8 activity is a non-invasive predictive biomarker candidate for progression and exacerbation of COPD. 相似文献
137.
Sugawara T Nakatsu D Kii H Maiya N Adachi A Yamamoto A Kano F Murata M 《Biochimica et biophysica acta》2012,1823(4):861-875
The ER-Golgi intermediate compartment (ERGIC) is an organelle through which cargo proteins pass and are being transferred by either anterograde or retrograde transport between the endoplasmic reticulum (ER) and the Golgi apparatus. We examined the effect of 80 different kinase inhibitors on ERGIC morphology and found that rottlerin, a PKCδ inhibitor, induced the dispersion of the perinuclear ERGIC into punctate structures. Rottlerin also delayed anterograde transport of vesicular stomatitis virus G protein (VSVG) from the ER to the Golgi and retrograde transport of cholera toxin from cell surface to the ER via the Golgi. RNA interference revealed that knockdown of PKCδ or ε resulted in the dispersion of the ERGIC, but unexpectedly did not inhibit VSVG and cholera toxin transport. We also found that rottlerin depolarized the mitochondrial membrane potential, as does carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), an uncoupler, and demonstrated that a decrease in the intracellular adenosine triphosphate (ATP) levels by rottlerin might underlie the block in transports. These results suggest that PKCδ and ε specifically regulate the morphology of the ERGIC and that the maintenance of ERGIC structure is not necessarily required for anterograde and retrograde transports. 相似文献
138.
139.
140.
Muacević-Katanec D Kekez T Fumić K Barić I Merkler M Jakić-Razumović J Krznarić Z Zadro R Katanec D Reiner Z 《Collegium antropologicum》2011,35(1):181-185
The clinical picture of classical homocystinuria is diverse. This is the first report of an adult homocystinuric patient with non-traumatic spontaneous small bowel perforation. A 47-year old man presented with abdominal rebound tenderness, hypotension and tachycardia, anemia, and elevated markers of inflammation. Other routine laboratory tests were normal. Abdominal x-ray showed no free air. An emergency laparotomy revealed jejunal perforation in the left upper quadrant. Histologic specimen showed full-thickness nonspecific inflammation of the intestinal wall with granulocytic infiltration, hemorrhage and necrosis. Tuberculosis, actinomycosis and typhus were histologically and clinically excluded. After excluding all known possible causes of perforation, we presumed a causative relationship between homocystinuria and small bowel perforation. It could be hypothesized that connective tissue weakness in homocystinuria is a result of homocysteine interference with recombinant human fibrillin-1 fragments or cross-linking of collagen through permanent degradation of disulfide bridges and lysine amino acid residues in proteins. DNA analysis showed three detectable mutations in the cystathionine beta-synthetase gene, 1278T:c.833T>C, and two new mutations, V372G:c.1133T > G, and D520G:c.1558A > G in the aternatively spliced exon 15. 相似文献