全文获取类型
收费全文 | 195篇 |
免费 | 23篇 |
出版年
2021年 | 4篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 7篇 |
2014年 | 5篇 |
2013年 | 31篇 |
2012年 | 3篇 |
2011年 | 12篇 |
2010年 | 8篇 |
2009年 | 8篇 |
2008年 | 8篇 |
2007年 | 5篇 |
2006年 | 5篇 |
2005年 | 15篇 |
2004年 | 7篇 |
2002年 | 6篇 |
2000年 | 6篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1992年 | 2篇 |
1989年 | 2篇 |
1975年 | 2篇 |
1943年 | 1篇 |
1929年 | 1篇 |
1926年 | 1篇 |
1925年 | 1篇 |
1924年 | 1篇 |
1921年 | 1篇 |
1920年 | 1篇 |
1915年 | 2篇 |
1914年 | 1篇 |
1909年 | 1篇 |
1902年 | 1篇 |
1901年 | 1篇 |
1897年 | 2篇 |
1892年 | 1篇 |
1891年 | 1篇 |
1889年 | 1篇 |
1888年 | 1篇 |
1887年 | 1篇 |
1883年 | 3篇 |
1882年 | 5篇 |
1881年 | 2篇 |
1880年 | 1篇 |
1879年 | 6篇 |
1878年 | 2篇 |
1877年 | 2篇 |
1876年 | 1篇 |
排序方式: 共有218条查询结果,搜索用时 15 毫秒
1.
2.
3.
4.
5.
6.
Jablonowski JA Chai W Li X Rudolph DA Murray WV Youngman MA Dax SL Nepomuceno D Bonaventure P Lovenberg TW Carruthers NI 《Bioorganic & medicinal chemistry letters》2004,14(5):1239-1242
Through SAR studies of a piperidinylindoline cinnamide HTS lead, the first potent, non-peptide, low molecular weight selective Neuropeptide Y Y2 (NPY Y2) antagonists have been synthesized. The SAR studies around the piperidinyl, the indolinyl, and the cinnamyl moieties are discussed. 相似文献
7.
The relevance of porphyrins as therapeutic drugs targeted to mitochondria has been widely recognized. In this work, we studied the action of meso-tetrakis porphyrins (TMPyP) on respiring rat liver mitochondria. Mn(III)TMPyP exerted a protective effect against lipid peroxidation induced by Fe(II) or the azo initiator 4,4-azobis(4-cyanopentanoic acid) (ABCPA), which partition in the hydrophobic phospholipid moiety, and 2,2-azobis(2-amidinepropane)dihydrochloride (ABAP), which partitions in the aqueous phase. In contrast, Fe(III)TMPyP itself induced an intense lipid peroxidation, accompanied by mitochondrial permeability transition. Both mesoporphyrins studied promoted a release of mitochondrial state-4 respiration, in the concentration range of 1.0–20 M. Based on the relative effects of Mn(III)TMPyP against ABAP and ABCPA-induced lipid peroxidation, we believe that meso-tetrakis porphyrins must concentrate preferably at membrane–water interfaces. 相似文献
8.
Mauricio de Mendonca SM Nepomuceno da Silva JL Cunha e-Silva N de Souza W Gazos Lopes U 《Gene》2000,243(1-2):179-185
Vesicle trafficking between organelles occurs through fusion of donor and specific acceptor membranes. This process is highly regulated and ensures proper direction in sorting and packaging of a number of molecules in eukaryotic cells. Monomeric GTPases of the Rab family play a pivotal role in the control of membrane fusion and vesicle traffic. In this paper, we characterize a Trypanosoma cruzi Rab 11 homologue (TcRab11) that shares at, the amino acid level, 40% similarity with human rab11, Arabdopsis thaliana rab11 and yeast rab11 homologue genes. Western blot analysis, using a polyclonal rabbit antiserum raised against a synthetic peptide derived from the COOH-terminus of predicted the TcRab11 protein, reacted to a 26kDa protein. In immunofluorescence assays, TcRab 11, was shown to be expressed in epimastigote and amastigote forms, but it was absent in trypomastigotes. Interestingly, the TcRab11 product seems to be located at the reservosome complex, a site of active endocytosis and vesicle fusion present only in the epimastigote stage. Therefore, TcRab11 may represent the first molecular marker of this peculiar organelle. 相似文献
9.
Bogan AA Dallas-Yang Q Ruse MD Maeda Y Jiang G Nepomuceno L Scanlan TS Cohen FE Sladek FM 《Journal of molecular biology》2000,302(4):831-851
Hepatocyte nuclear factor 4alpha (HNF4alpha) (NR2A1), an orphan member of the nuclear receptor superfamily, binds DNA exclusively as a homodimer even though it is very similar in amino acid sequence to retinoid X receptor alpha (RXRalpha), which heterodimerizes readily with other receptors. Here, experimental analysis of residues involved in protein dimerization and studies on a reported ligand for HNF4alpha are combined with a structural model of the HNF4alpha ligand-binding domain (LBD) (residues 137 to 384). When K300 (in helix 9) and E327 (in helix 10) of HNF4alpha1 were converted to the analogous residues in RXRalpha (E390 and K417, respectively) the resulting construct did not heterodimerize with the wild-type HNF4alpha, although it was still able to form homodimers and bind DNA. Furthermore, the double mutant did not heterodimerize with RXR or RAR but was still able to dimerize in solution with an HNF4alpha construct truncated at amino acid residue 268. This suggests that the charge compatibility between helices 9 and 10 is necessary, but not sufficient, to determine dimerization partners, and that additional residues in the HNF4alpha LBD are also important in dimerization. The structural model of the HNF4alpha LBD and an amino acid sequence alignment of helices 9 and 10 in various HNF4 and other receptor genes indicates that a K(X)(26)E motif can be used to identify HNF4 genes from other organisms and that a (E/D(X)(26-29)K/R) motif can be used to predict heterodimerization of many, but not all, receptors with RXR. In vitro analysis of another HNF4alpha mutant construct indicates that helix 10 also plays a structural role in the conformational integrity of HNF4alpha. The structural model and experimental analysis indicate that fatty acyl CoA thioesters, the proposed HNF4alpha ligands, are not good candidates for a traditional ligand for HNF4alpha. Finally, these results provide insight into the mechanism of action of naturally occurring mutations in the human HNF4alpha gene found in patients with maturity onset diabetes of the young 1 (MODY1). 相似文献