全文获取类型
收费全文 | 950篇 |
免费 | 63篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 19篇 |
2020年 | 5篇 |
2019年 | 13篇 |
2018年 | 26篇 |
2017年 | 17篇 |
2016年 | 31篇 |
2015年 | 50篇 |
2014年 | 54篇 |
2013年 | 88篇 |
2012年 | 72篇 |
2011年 | 81篇 |
2010年 | 65篇 |
2009年 | 51篇 |
2008年 | 56篇 |
2007年 | 61篇 |
2006年 | 57篇 |
2005年 | 52篇 |
2004年 | 34篇 |
2003年 | 47篇 |
2002年 | 46篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 9篇 |
1994年 | 9篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有1013条查询结果,搜索用时 31 毫秒
81.
82.
83.
84.
The peculiar heme pocket of the 2/2 hemoglobin of cold-adapted Pseudoalteromonas haloplanktis TAC125
Barry D. Howes Daniela Giordano Leonardo Boechi Roberta Russo Simona Mucciacciaro Chiara Ciaccio Federica Sinibaldi Maria Fittipaldi Marcelo A. Mart�� Dar��o A. Estrin Guido di Prisco Massimo Coletta Cinzia Verde Giulietta Smulevich 《Journal of biological inorganic chemistry》2011,16(2):299-311
The genome of the cold-adapted bacterium Pseudoalteromonas haloplanktis TAC125 contains multiple genes encoding three distinct monomeric hemoglobins exhibiting a 2/2 ??-helical fold. In the present work, one of these hemoglobins is studied by resonance Raman, electronic absorption and electronic paramagnetic resonance spectroscopies, kinetic measurements, and different bioinformatic approaches. It is the first cold-adapted bacterial hemoglobin to be characterized. The results indicate that this protein belongs to the 2/2 hemoglobin family, Group II, characterized by the presence of a tryptophanyl residue on the bottom of the heme distal pocket in position G8 and two tyrosyl residues (TyrCD1 and TyrB10). However, unlike other bacterial hemoglobins, the ferric state, in addition to the aquo hexacoordinated high-spin form, shows multiple hexacoordinated low-spin forms, where either TyrCD1 or TyrB10 can likely coordinate the iron. This is the first example in which both TyrCD1 and TyrB10 are proposed to be the residues that are alternatively involved in heme hexacoordination by endogenous ligands. 相似文献
85.
Vacca F D'Ambrosi N Nestola V Amadio S Giustizieri M Cucchiaroni ML Tozzi A Velluz MC Mercuri NB Volonté C 《Glycobiology》2011,21(5):634-643
N-Glycosylation affects the function of ion channels at the level of multisubunit assembly, protein trafficking, ligand binding and channel opening. Like the majority of membrane proteins, ionotropic P2X receptors for extracellular ATP are glycosylated in their extracellular moiety. Here, we used site-directed mutagenesis to the four predicted N-glycosylation sites of P2X(3) receptor (Asn(139), Asn(170), Asn(194) and Asn(290)) and performed comparative analysis of the role of N-glycans on protein stability, plasma membrane delivery, trimer formation and inward currents. We have found that in transiently transfected HEK293 cells, Asn(170) is apparently the most important site for receptor stability, since its mutation causes a primary loss in protein content and indirect failure in membrane expression, oligomeric association and inward current responses. Even stronger effects are obtained when mutating Thr(172) in the same glycosylation consensus. Asn(194) and Asn(290) are the most dispensable, since even their simultaneous mutation does not affect any tested receptor feature. All double mutants containing Asn(170) mutation or the Asn(139)/Asn(290) double mutant are instead almost unable to assemble into a functional trimeric structure. The main emerging finding is that the inability to assemble into trimers might account for the impaired function in P2X(3) mutants where residue Asn(170) is replaced. These results improve our knowledge about the role of N-glycosylation in proper folding and oligomeric association of P2X(3) receptor. 相似文献
86.
Simoni D Rondanin R Marchetti P Rullo C Baruchello R Grisolia G Barbato G Giovannini R Marchioro C Capelli AM Virginio C Bozzoli A Borea PA Merighi S Donati D 《Bioorganic & medicinal chemistry letters》2011,21(18):5423-5427
The introduction of the isoxazole ring as bioisosteric replacement of the acetyl group of anatoxin-a led to a new series of derivatives binding to nicotinic acetylcholine receptors. Bulkier substitutions than methyl at the 3 position of isoxazole were shown to be detrimental for the activity. The binding potency of the most interesting compounds with α1, α7 and α3β4 receptor subtypes, was, anyway, only at micromolar level. Moreover, differently from known derivatives with pyridine, isoxazole condensed to azabicyclo ring led to no activity. 相似文献
87.
Antonella?CalogeroEmail author Antonio?Porcellini Vincenza?Lombari Cinzia?Fabbiano Antonietta?Arcella Massimo?Miscusi Donatella?Ponti Giuseppe?Ragona 《Cancer cell international》2011,11(1):5
Background
Less than 30% of malignant gliomas respond to adjuvant chemotherapy. Here, we have asked whether variations in the constitutive expression of early-growth response factor 1 (EGR-1) predicted acute cytotoxicity and clonogenic cell death in vitro, induced by six different chemotherapics. 相似文献88.
Riccio A Mangiapia G Giordano D Flagiello A Tedesco R Bruno S Vergara A Mazzarella L di Prisco G Pucci P Paduano L Verde C 《IUBMB life》2011,63(5):346-354
In vitro, and possibly in vivo, hemoglobin polymerization and red blood cell sickling appear to be widespread in codfish. In this article, we show that the hemoglobins of the two Arctic fish Lycodes reticulatus and Gadus morhua also have the tendency to polymerize, as monitored by dynamic light scattering experiments. The elucidation of the primary structure of the single hemoglobin of the zoarcid L. reticulatus shows the presence of a large number of cysteyl residues in α and β chains. Their role in eliciting the ability to produce polymers was also addressed by MALDI-TOF and TOF-TOF mass spectrometry. The G.morhua globins are also rich in Cys, but unlike in L. reticulatus, polymerization does not seem to be disulfide driven. The widespread occurrence of the polymerization phenomenon displayed by hemoglobins of Arctic fish supports the hypothesis that this feature may bea response to stressful environmental conditions. 相似文献
89.
Shafat I Ben-Arush MW Issakov J Meller I Naroditsky I Tortoreto M Cassinelli G Lanzi C Pisano C Ilan N Vlodavsky I Zunino F 《Journal of cellular and molecular medicine》2011,15(9):1857-1864
Heparanase is an endoglycosidase that specifically cleaves heparan sulphate side chains of heparan sulphate proteoglycans, activity that is strongly implicated in cell migration and invasion associated with tumour metastasis, angiogenesis and inflammation. Heparanase up-regulation was documented in an increasing number of human carcinomas, correlating with reduced post-operative survival rate and enhanced tumour angiogenesis. Expression and significance of heparanase in human sarcomas has not been so far reported. Here, we applied the Ewing's sarcoma cell line TC71 and demonstrated a potent inhibition of cell invasion in vitro and tumour xenograft growth in vivo upon treatment with a specific inhibitor of heparanase enzymatic activity (compound SST0001, non-anticoagulant N-acetylated, glycol split heparin). Next, we examined heparanase expression and cellular localization by immunostaining of a cohort of 69 patients diagnosed with Ewing's sarcoma. Heparanase staining was noted in all patients. Notably, heparanase staining intensity correlated with increased tumour size (P = 0.04) and with patients' age (P = 0.03), two prognostic factors associated with a worse outcome. Our study indicates that heparanase expression is induced in Ewing's sarcoma and associates with poor prognosis. Moreover, it encourages the inclusion of heparanase inhibitors (i.e. SST0001) in newly developed therapeutic modalities directed against Ewing's sarcoma and likely other malignancies. 相似文献
90.