全文获取类型
收费全文 | 239篇 |
免费 | 13篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2021年 | 3篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 15篇 |
2014年 | 14篇 |
2013年 | 12篇 |
2012年 | 19篇 |
2011年 | 18篇 |
2010年 | 11篇 |
2009年 | 8篇 |
2008年 | 13篇 |
2007年 | 12篇 |
2006年 | 7篇 |
2005年 | 4篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 10篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 8篇 |
1989年 | 3篇 |
1988年 | 8篇 |
1987年 | 1篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1981年 | 1篇 |
1978年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有252条查询结果,搜索用时 31 毫秒
31.
Kinetic evidence for a role of heme geometry on the modulation of carbon monoxide reactivity in human hemoglobin 总被引:1,自引:0,他引:1
Kinetics of CO binding to human hemoglobin (Hb) has been followed below neutrality. With respect to the behavior observed at pH 7.0, CO binding to deoxy-Hb at pH 2.3 displays a much faster second-order combination rate constant (1.2 x 10(-7) M-1 s-1) and loss of the autocatalytic character of the kinetic progress curve. The spectroscopic features of the transient deoxy-Hb at pH 2.75 indicate the phenomenon to be related to the cleavage of the proximal histidine N epsilon-Fe bond, as reported for monomeric hemoproteins (Coletta, M., Ascenzi, P., Traylor, T. G., and Brunori, M. (1985) J. Biol. Chem. 260, 4151-4155). The faster CO binding rate constant, higher than that characteristic of the R state, cannot be attributed to either (i) an enhanced dimerization of deoxy-Hb at low pH, or (ii) a quaternary switch of the unliganded form to the R0 state. The data indicate that interaction(s) of the heme on the proximal side is crucial in accounting for the difference in the CO binding rate constant between the two quaternary conformations of hemoglobin. 相似文献
32.
Massimo Coletta Paolo Ascenzi Laura Bravin Gino Amiconi Martino Bolognesi Mario Guarneri 《Journal of biomolecular structure & dynamics》2013,31(4):959-972
Abstract The effect of activating dipeptides, sequentially homologous to the Ile 16-Val 17 N-terminus of bovine β-trypsin (β-trypsin), on equilibria involved in the binding of strong ligands (i.e., n-butylamine, the bovine basic pancreatic trypsin inhibitor (Kunitz-type inhibitor; BPTI) and the porcine pancreatic secretory trypsin inhibitor (Kazal-type inhibitor, type I; PSTI)) to bovine trypsinogen (trypsinogen) was investigated at pH 5.5 (I = 0.1 M) and T = 21.0 ± 0.5°C; under the same experimental conditions, thermodynamics for the binding of strong ligands to β-trypsin was also obtained. The equilibria involved in the binding of activating dipeptides and/or inhibitors to β-trypsin and to its zymogen are described according to an induced-fit formalism, taking into account ligand-linked interaction(s) between different functional and structural domains of the (pro)enzyme possibly involved in the trypsinogen-to-β-trypsin activation pathway. The analysis of data is focussed on parameters describing interactions between the so-called Ile-Val pocket (where the Ile16-Val17/V-terminus of β-trypsin or activating dipeptides bind) and the primary and/or secondary recognition subsite(s) (where strong ligands associate) present in the (pro)enzyme. Such an analysis allows to dissect the contributions due to the primary recognition subsite, where small mono-functional ligands (e.g., n-butylamine) bind, from those of the secondary subsite(s), which are additional recognition clefts for macromolecular inhibitors (e.g., BPTI and PSTI). 相似文献
33.
A M Cianciulli R Bovani C Leonardo F Iori A M Coletta R Marzano A Antenucci G M Gandolfo C Laurenti 《European journal of histochemistry : EJH》2001,45(1):65-71
We evaluated the genetic changes in bladder cancer biopsy by fluorescence in situ hybridization (FISH) and related them to stage and grade of the tumor, ploidy (FCM) and clinical outcome, to determine a simple method to identify tumors with a poorer prognosis. Using FISH the numerical aberrations of chromosomes 1, 7, 9, 17 in tumor's imprints of 70 patients with transitional cell cancer (TCC) were determined. First of all, the data demonstrated that the sensitivity of FISH in detecting quantitative DNA aberrations exceeds FCM's sensitivity. The frequency of chromosome 1 and 9 aberrations did not show significant differences in diploid and aneuploid tumors in different stage and grade. On the contrary, the chromosome 7 and 17 aneusomy showed greater differences between pT1 and pT2-3 tumors (p<0.032 and p<0.0006, respectively) than between stage pTa and pT1. In our investigation, an increasing number of aberrations was observed in all chromosomes examined in tumors of patients who afterwards underwent cystectomy and/or had recurrent tumors. These results suggest that chromosome 7 and 17 aneusomy could be predictive of adverse outcome in a subgroup of patients with superficial tumors at presentation. 相似文献
34.
35.
Gabriella Fanali Giampiero De Sanctis Magda Gioia Massimo Coletta Paolo Ascenzi Mauro Fasano 《Journal of biological inorganic chemistry》2009,14(2):209-217
Human serum albumin (HSA) participates in heme scavenging, the bound heme turning out to be a reactivity center and a powerful
spectroscopic probe. Here, the reversible unfolding of heme–HSA has been investigated by 1H-NMR relaxometry, circular dichroism, and absorption spectroscopy. In the presence of 6 equiv of myristate (thus fully saturating
all available fatty acid binding sites in serum heme–albumin), 1.0 M guanidinium chloride induces some unfolding of heme–HSA,
leading to the formation of a folding intermediate; this species is characterized by increased relaxivity and enhanced dichroism
signal in the Soret region, suggesting a more compact heme pocket conformation. Heme binds to the folding intermediate with
K
d = (1.2 ± 0.1) × 10−6 M. In the absence of myristate, the conformation of the folding intermediate state is destabilized and heme binding is weakened
[K
d = (3.4 ± 0.1) × 10−5 M]. Further addition of guanidinium chloride (up to 5 M) brings about the usual denaturation process. In conclusion, myristate
protects HSA from unfolding, stabilizing a folding intermediate state in equilibrium with the native and the fully unfolded
protein, envisaging a two-step unfolding pathway for heme–HSA in the presence of myristate. 相似文献
36.
Chiara Ciaccio Grazia R. Tundo Giuseppe Grasso Daniela Marasco Magda Gioia Massimo Coletta 《Journal of molecular biology》2009,385(5):1556-1567
Insulin-degrading enzyme (IDE) is an interesting pharmacological target for Alzheimer's disease (AD), since it hydrolyzes β-amyloid, producing non-neurotoxic fragments. It has also been shown that the somatostatin level reduction is a pathological feature of AD and that it regulates the neprilysin activity toward β-amyloid.In this work, we report for the first time that IDE is able to hydrolyze somatostatin [kcat (s− 1) = 0.38 (± 0.05); Km (M) = 7.5 (± 0.9) × 10− 6] at the Phe6-Phe7 amino acid bond. On the other hand, somatostatin modulates IDE activity, enhancing the enzymatic cleavage of a novel fluorogenic β-amyloid through a decrease of the Km toward this substrate, which corresponds to the 10-25 amino acid sequence of the Aβ(1-40). Circular dichroism spectroscopy and surface plasmon resonance imaging experiments show that somatostatin binding to IDE brings about a concentration-dependent structural change of the secondary and tertiary structure(s) of the enzyme, revealing two possible binding sites. The higher affinity binding site disappears upon inactivation of IDE by ethylenediaminetetraacetic acid, which chelates the catalytic Zn2+ ion. As a whole, these features suggest that the modulatory effect is due to an allosteric mechanism: somatostatin binding to the active site of one IDE subunit (where somatostatin is cleaved) induces an enhancement of IDE proteolytic activity toward fluorogenic β-amyloid by another subunit. Therefore, this investigation on IDE-somatostatin interaction contributes to a more exhaustive knowledge about the functional and structural aspects of IDE and its pathophysiological implications in the amyloid deposition and somatostatin homeostasis in the brain. 相似文献
37.
Alessandra Pesce Liesbet Thijs Marco Nardini Lorenza Sisinni Louise Gourlay Massimiliano Coletta Xuehua Wan Paolo Ascenzi Martino Bolognesi 《Journal of molecular biology》2009,386(1):246-35534
Among heme-based sensors, recent phylogenomic and sequence analyses have identified 34 globin coupled sensors (GCS), to which an aerotactic or gene-regulating function has been tentatively ascribed. Here, the structural and biochemical characterization of the globin domain of the GCS from Geobacter sulfurreducens (GsGCS162) is reported. A combination of X-ray crystallography (crystal structure at 1.5 Å resolution), UV-vis and resonance Raman spectroscopy reveals the ferric GsGCS162 as an example of bis-histidyl hexa-coordinated GCS. In contrast to the known hexa-coordinated globins, the distal heme-coordination in ferric GsGCS162 is provided by a His residue unexpectedly located at the E11 topological site. Furthermore, UV-vis and resonance Raman spectroscopy indicated that ferrous deoxygenated GsGCS162 is a penta-/hexa-coordinated mixture, and the heme hexa-to-penta-coordination transition does not represent a rate-limiting step for carbonylation kinetics. Lastly, electron paramagnetic resonance indicates that ferrous nitrosylated GsGCS162 is a penta-coordinated species, where the proximal HisF8-Fe bond is severed. 相似文献
38.
Ricardo D Coletta Erica L McCoy Valerie Burns Kiyoshi Kawakami James L McManaman John J Wysolmerski Heide L Ford 《BMC developmental biology》2010,10(1):4
Background
The Six1 homeobox gene is highly expressed in the embryonic mammary gland, continues to be expressed in early postnatal mammary development, but is lost when the mammary gland differentiates during pregnancy. However, Six1 is re-expressed in breast cancers, suggesting that its re-instatement in the adult mammary gland may contribute to breast tumorigenesis via initiating a developmental process out of context. Indeed, recent studies demonstrate that Six1 overexpression in the adult mouse mammary gland is sufficient for initiating invasive carcinomas, and that its overexpression in xenograft models of mammary cancer leads to metastasis. These data demonstrate that Six1 is causally involved in both breast tumorigenesis and metastasis, thus raising the possibility that it may be a viable therapeutic target. However, because Six1 is highly expressed in the developing mammary gland, and because it has been implicated in the expansion of mammary stem cells, targeting Six1 as an anti-cancer therapy may have unwanted side effects in the breast. 相似文献39.
Paolo Ascenzi Loris Leboffe Alessandra Pesce Chiara Ciaccio Diego Sbardella Martino Bolognesi Massimo Coletta 《PloS one》2014,9(5)
Within the globin superfamily, protoglobins (Pgb) belong phylogenetically to the same cluster of two-domain globin-coupled sensors and single-domain sensor globins. Multiple functional roles have been postulated for Methanosarcina acetivorans Pgb (Ma-Pgb), since the detoxification of reactive nitrogen and oxygen species might co-exist with enzymatic activity(ies) to facilitate the conversion of CO to methane. Here, the nitrite-reductase and peroxynitrite isomerization activities of the CysE20Ser mutant of Ma-Pgb (Ma-Pgb*) are reported and analyzed in parallel with those of related heme-proteins. Kinetics of nitrite-reductase activity of ferrous Ma-Pgb* (Ma-Pgb*-Fe(II)) is biphasic and values of the second-order rate constant for the reduction of NO2
– to NO and the concomitant formation of nitrosylated Ma-Pgb*-Fe(II) (Ma-Pgb*-Fe(II)-NO) are k
app1 = 9.6±0.2 M–1 s–1 and k
app2 = 1.2±0.1 M–1 s–1 (at pH 7.4 and 20°C). The k
app1 and k
app2 values increase by about one order of magnitude for each pH unit decrease, between pH 8.3 and 6.2, indicating that the reaction requires one proton. On the other hand, kinetics of peroxynitrite isomerization catalyzed by ferric Ma-Pgb* (Ma-Pgb*-Fe(III)) is monophasic and values of the second order rate constant for peroxynitrite isomerization by Ma-Pgb*-Fe(III) and of the first order rate constant for the spontaneous conversion of peroxynitrite to nitrate are h
app = 3.8×104 M–1 s–1 and h
0 = 2.8×10–1 s–1 (at pH 7.4 and 20°C). The pH-dependence of h
on and h
0 values reflects the acid-base equilibrium of peroxynitrite (pK
a = 6.7 and 6.9, respectively; at 20°C), indicating that HOONO is the species that reacts preferentially with the heme-Fe(III) atom. These results highlight the potential role of Pgbs in the biosynthesis and scavenging of reactive nitrogen and oxygen species. 相似文献
40.
Daniela C. Granato Mariana R. Zanetti Rebeca Kawahara Sami Yokoo Romênia R. Domingues Annelize Z. Arag?o Michelle Agostini Marcelo F. Carazzolle Ramon O. Vidal Isadora L. Flores Johanna Korvala Nilva K. Cervigne Alan R. S. Silva Ricardo D. Coletta Edgard Graner Nicholas E. Sherman Adriana F. Paes Leme 《PloS one》2014,9(5)
Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules. 相似文献