全文获取类型
收费全文 | 221篇 |
免费 | 10篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 14篇 |
2014年 | 13篇 |
2013年 | 14篇 |
2012年 | 18篇 |
2011年 | 17篇 |
2010年 | 18篇 |
2009年 | 11篇 |
2008年 | 19篇 |
2007年 | 9篇 |
2006年 | 11篇 |
2005年 | 12篇 |
2004年 | 9篇 |
2003年 | 4篇 |
2002年 | 1篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1977年 | 4篇 |
1975年 | 1篇 |
排序方式: 共有231条查询结果,搜索用时 15 毫秒
161.
Soares AM Marcussi S Stábeli RG França SC Giglio JR Ward RJ Arantes EC 《Biochemical and biophysical research communications》2003,302(2):193-200
A protein, which neutralizes the enzymatic, toxic, and pharmacological activities of various basic and acidic phospholipases A(2) from the venoms of Bothrops moojeni, Bothrops pirajai, and Bothrops jararacussu, was isolated from B. moojeni snake plasma by affinity chromatography using immobilized myotoxins on Sepharose gel. Biochemical characterization of this myotoxin inhibitor protein (BmjMIP) showed it to be an oligomeric glycoprotein with a M(r) of 23,000-25,000 for the monomeric subunit. BmjMIP was stable in the pH range from 4.0 to 12.0, between 4 and 80 degrees C, even after deglycosylation. The role of the carbohydrate moiety was investigated and found not to affect the in vitro function of the inhibitor. The corresponding 500bp cDNA obtained by RT-PCR from the liver of the snake encodes a mature protein of 166 amino acid residues including a 19 amino acid signal peptide. The primary structure of BmjMIP showed a high similarity with other snake phospholipase A(2) inhibitors (PLIs) in which the carbohydrate recognition domain (CRD) and the glycosylation site (Asn103) are conserved. Circular dichroism spectroscopy indicated that no significant alterations in the secondary structure of either the BmjMIP or the target protein occur upon their interaction. BmjMIP has a wide range of inhibitory properties against basic and acidic PLA(2)s from Bothrops venoms (anti-enzymatic, anti-myotoxic, anti-edema inducing, anti-cytotoxic, anti-bactericidal, and anti-lethal). However, the inhibitor showed a reduced ability to neutralize the biological activities of crotoxin B (CB), the PLA(2) homologue associated with crotapotin in Crotalus durissus terrificus snake venom. Finally, the purified PLA(2) inhibitor was shown to protect in vivo against the toxic and pharmacological effects of a homologous PLA(2) enzyme, suggesting that PLIs or a corresponding derived peptide may prove useful in the treatment of snakebite victims or, more importantly, in the treatment of the many human diseases in which these enzymes have been implicated. 相似文献
162.
Cecchini AL Soares AM Cecchini R de Oliveira AH Ward RJ Giglio JR Arantes EC 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2004,138(4):429-436
Myonecrosis, in addition to edema and other biological manifestations, are conspicuous effects of Bothrops snake venoms, some of them caused by phospholipases A(2) (PLA(2)s). Asp49-PLA(2)s are catalytically active, whereas Lys49-PLA(2)s, although highly toxic, have little or no enzymatic activity upon artificial substrates, due to a substitution of lysine for aspartic acid at position 49. Crotapotin (CA), the acidic counterpart of crotoxin PLA(2) (CB), is a PLA(2)-like protein from Crotalus durissus terrificus snake venom, and is considered a chaperone protein for CB, able to increase its lethality about ten fold, but to inhibit the formation of the rat paw edema induced by carrageenin and by snake venoms. In this study, we demonstrate that CA significantly inhibits the edema induced by BthTX-I (23% inhibition), BthTX-II (27%), PrTX-I (25%), PrTX-III (35%) and MjTX-II (10%) on the mouse paw. CK levels evoked by isolated Asp49 or Lys49-PLA(2)s were reduced by 40% to 54% in the presence of CA and, in all cases, the membrane damaging activity of the toxins was also reduced. Circular dichroism spectra of the PLA(2)s in the presence and absence of CA showed that there was not any detectable secondary structural modification due to association between CA and the myotoxins. However, Fourier Transformed Infrared (FT-IR) analysis indicated that ionic and hydrophobic contacts contributed to stabilize this interaction. 相似文献
163.
164.
Patients with severe and complicated paracoccidioidomycosis are treated with amphotericin B by the intravenous route. Fluconazole
is active in vitro against Paracoccidioides brasiliensis and can also be administered intravenously, but few clinical or experimental data are available about its action against
the infection caused by this fungus. In the present study, the efficacy of fluconazole andamphotericin B was assessed comparatively
in rats inoculated parenterally with P. brasiliensis. The treatment was performed 3 times a week for 4 weeks starting one week after infection. Fluconazole administered intraperitoneally
(14 mg/kg bodyweight/dose) was more effective (P > 0.001)than amphotericin B (2 mg/kg body weight/dose) in reducing the number
of colony forming units in the lungs and spleen. When administered intravenously at the dose of 3 mg/kg body weight, fluconazole
was as effective as amphotericin B (0.8 mg/kg body weight) in reducing the pulmonary fungal burden. Under these conditions,
the rats treated with fluconazole had a smaller number of colony forming units than untreated animals (P > 0.001), but amphotericin
B was more effective than fluconazole in reducing spleen infection (P > 0.005). Except for this result obtained with a low
dose, fluconazole showed an antifungal action equal to or higher than that of amphotericin B. The activity of fluconazole
at doses equivalent to those used for human treatment suggests that this antifungal agent may be an alternative to amphotericin
B for the early intravenous treatment of patients with paracoccidioidomycosis.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
165.
Astringency of aqueous solutions of phenolic compounds (grape seed tannins,
tannic acid, catechin and gallic acid) increased upon addition of citric
acid, whereas the astringency of alum was reduced. Astringency of alum was
decreased equivalently by addition of equi-sour levels of lactic acid,
citric acid or hydrochloric acid. The difference between alum and the
phenolic compounds is speculated to result from chemical modifications
affecting binding of the astringents with oral proteins rather than
cognitive differences. Chelation of the aluminum ion in alum by acids
reduces its availability for interacting with salivary proteins or
epithelial proteins. In contrast, the increased astringency produced upon
acidification of phenolic compounds is speculated to result from the pH
driven increase in the affinity of the phenols for binding with proteins.
These results suggest that alum cannot be used interchangeably with
phenolic astringents in psychophysical studies.
相似文献
166.
This report describes a lysozyme expressed at high levels in the stomach of
the hoatzin, the only known foregut-fermenting bird. Evolutionary
comparison places it among the calcium-binding lysozymes rather than among
the conventional types. Conventional lysozymes were recruited as digestive
enzymes twice in the evolution of mammalian foregut fermenters, and these
independently recruited lysozymes share convergent structural changes
attributed to selective pressures in the stomach. Biochemical convergence
and parallel amino acid replacements are observed in the hoatzin stomach
lysozyme even though it has a different genetic origin from the mammalian
examples and has undergone more than 300 million years of independent
evolution.
相似文献
167.
Gabriel C. G. Mello Marcella L. Santos Fábio P. Arantes Thiago C. Pessali Marcelo F. G. Brito José E. Santos 《Acta zoologica》2019,100(1):14-23
The anatomical arrangement of the digestive tract and the length (cm) of the oesophagus and intestine of the catfish Lophiosilurus alexandri were described, and the intestinal coefficient was determined. L. alexandri oesophagus is short, in median position, and presents longitudinally folded mucosa, whilst its epithelium is stratified and non-keratinised, with mucous, claviform and epithelial cells. Stomach has “C” shape, with folded mucosa along cardiac region, disordered in the fundic region, and directed to the sphincter in the pyloric region. Its epithelium is simple prismatic, and cardiac and fundic portions have gastric glands. Cranial intestine is formed by pyloric flexure and descending loop attached to the right side of stomach. Middle intestine is winding and positioned to the right of caudal portion of stomach. Caudal intestine is linear and with a median position up to the anus. Intestinal coefficient was 1.39 ± 0.30 cm. Epithelium is simple prismatic with brush border and contains epithelial and goblet cells. Caudal region has highest concentration of goblet cells. Were detected neutral glycoproteins, carboxylated and sulphated acid glycoconjugates for mucous cells and goblet cells, and neutral glycoproteins for the apical region of gastric epithelial cells. Morphological features could be related to piscivorous species feeding habit. 相似文献
168.
Keith Gourlay Jinguang Hu Valdeir Arantes Merja Penttil? Jack N. Saddler 《The Journal of biological chemistry》2015,290(5):2938-2945
Although the actions of many of the hydrolytic enzymes involved in cellulose hydrolysis are relatively well understood, the contributions that amorphogenesis-inducing proteins might contribute to cellulose deconstruction are still relatively undefined. Earlier work has shown that disruptive proteins, such as the non-hydrolytic non-oxidative protein Swollenin, can open up and disaggregate the less-ordered regions of lignocellulosic substrates. Within the cellulosic fraction, relatively disordered, amorphous regions known as dislocations are known to occur along the length of the fibers. It was postulated that Swollenin might act synergistically with hydrolytic enzymes to initiate biomass deconstruction within these dislocation regions. Carbohydrate binding modules (CBMs) that preferentially bind to cellulosic substructures were fluorescently labeled. They were imaged, using confocal microscopy, to assess the distribution of crystalline and amorphous cellulose at the fiber surface, as well as to track changes in surface morphology over the course of enzymatic hydrolysis and fiber fragmentation. Swollenin was shown to promote targeted disruption of the cellulosic structure at fiber dislocations. 相似文献
169.
170.
Rodrigues CM Valadares HM Francisco AF Arantes JM Campos CF Teixeira-Carvalho A Martins-Filho OA Araujo MS Arantes RM Chiari E Franco GR Machado CR Pena SD Faria AM Macedo AM 《PLoS neglected tropical diseases》2010,4(10):e846
A century after the discovery of Trypanosoma cruzi in a child living in Lassance, Minas Gerais, Brazil in 1909, many uncertainties remain with respect to factors determining the pathogenesis of Chagas disease (CD). Herein, we simultaneously investigate the contribution of both host and parasite factors during acute phase of infection in BALB/c mice infected with the JG and/or CL Brener T. cruzi strains. JG single infected mice presented reduced parasitemia and heart parasitism, no mortality, levels of pro-inflammatory mediators (TNF-α, CCL2, IL-6 and IFN-γ) similar to those found among naïve animals and no clinical manifestations of disease. On the other hand, CL Brener single infected mice presented higher parasitemia and heart parasitism, as well as an increased systemic release of pro-inflammatory mediators and higher mortality probably due to a toxic shock-like systemic inflammatory response. Interestingly, coinfection with JG and CL Brener strains resulted in intermediate parasitemia, heart parasitism and mortality. This was accompanied by an increase in the systemic release of IL-10 with a parallel increase in the number of MAC-3+ and CD4+ T spleen cells expressing IL-10. Therefore, the endogenous production of IL-10 elicited by coinfection seems to be crucial to counterregulate the potentially lethal effects triggered by systemic release of pro-inflammatory mediators induced by CL Brener single infection. In conclusion, our results suggest that the composition of the infecting parasite population plays a role in the host response to T. cruzi in determining the severity of the disease in experimentally infected BALB/c mice. The combination of JG and CL Brener was able to trigger both protective inflammatory immunity and regulatory immune mechanisms that attenuate damage caused by inflammation and disease severity in BALB/c mice. 相似文献