全文获取类型
收费全文 | 440篇 |
免费 | 24篇 |
出版年
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 10篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 11篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 33篇 |
2014年 | 27篇 |
2013年 | 30篇 |
2012年 | 37篇 |
2011年 | 33篇 |
2010年 | 15篇 |
2009年 | 22篇 |
2008年 | 26篇 |
2007年 | 19篇 |
2006年 | 20篇 |
2005年 | 16篇 |
2004年 | 16篇 |
2003年 | 14篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 10篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1934年 | 1篇 |
排序方式: 共有464条查询结果,搜索用时 968 毫秒
91.
Cavasini CE De Mattos LC Alves RT Couto AA Calvosa VS Domingos CR Castilho L Rossit AR Machado RL 《Human biology; an international record of research》2006,78(2):215-219
We compared the serological phenotypic frequencies of ABO, MNSs, and Duffy in 417 blood donors and 309 malaria patients from four Brazilian Amazon areas. Our results suggest no correlation between ABO phenotype and malaria infection in all areas studied. We observed significant correlation between the S +s +, S +s -, and S -s + phenotypes and malaria infection in three areas. Some of the Duffy phenotypes showed significant correlation between donors and malaria patients in different areas. These data are an additional contribution to the establishment of differential host susceptibility to malaria. 相似文献
92.
Rocha R Leal SS Teixeira VH Regalla M Huber H Baptista AM Soares CM Gomes CM 《Biochemistry》2006,45(34):10376-10384
Zinc centers play a key role as important structure determinants in a variety of proteins including ferredoxins (Fd). Here, we exploit the availability of two highly similar ferredoxin isoforms from the thermophile Sulfolobus metallicus, which differ in the residues involved in coordinating a His/Asp zinc site that ties together the protein core with its N-terminal extension, to investigate the effect of the absence of this site on ferredoxin folding. The conformational properties of the zinc-containing (FdA) and zinc-lacking (FdB) isoforms were investigated using visible absorption and tryptophan fluorescence emission. Fluorescence quenching studies, together with comparative modeling and molecular dynamics simulations, indicate that the FdB N-terminal extension assumes a fold identical to that of the Zn(2+)-containing isoform. The thermal stability of the isoforms was investigated in a broad pH range (2 < pH < 10), and at physiological pH conditions, both proteins unfold above 100 degrees C. Surprisingly, the Zn(2+)-lacking isoform was always found to be more stable than its Zn(2+)-containing counterpart: a DeltaT(m) approximately 9 degrees C is determined at pH 7, a difference that becomes even more significant at extreme pH values, reaching a DeltaT(m) approximately 24 degrees C at pH 2 and 10. The contribution of the Zn(2+) site to ferredoxin stability was further resolved using selective metal chelators. During thermal unfolding, the zinc scavenger TPEN significantly lowers the T(m) in FdA ( approximately 10 degrees C), whereas it has no effect in FdB. This shows that the Zn(2+) site contributes to ferredoxin stability but that FdB has devised a structural strategy that accounts for an enhanced stability without using a metal cross-linker. An analysis of the FdB sequence and structural model leads us to propose that the higher stability of the zinc-containing ferredoxin results from van der Waals contacts formed between the residues that occupy the same spatial region where the zinc ligands are found in FdA. These favor the formation of a novel local stabilizing hydrophobic core and illustrate a strategy of natural fold design. 相似文献
93.
Rodrigues ML Archer M Martel P Miranda S Thomaz M Enguita FJ Baptista RP Pinho e Melo E Sousa N Cravador A Carrondo MA 《Biochimica et biophysica acta》2006,1764(1):110-121
The crystal structure of the elicitin beta-cinnamomin (beta-CIN) was determined in complex with ergosterol at 1.1 A resolution. beta-CIN/ergosterol complex crystallized in the monoclinic space group P2(1), with unit cell parameters of a = 31.0, b = 62.8, c = 50.0 A and beta = 93.4 degrees and two molecules in the asymmetric unit. Ligand extraction with chloroform followed by crystallographic analysis yielded a 1.35 A structure of beta-CIN (P4(3)2(1)2 space group) where the characteristic elicitin fold was kept. After incubation with cholesterol, a new complex structure was obtained, showing that the protein retains, after the extraction procedure, its ability to complex sterols. The necrotic effect of beta-CIN on tobacco was also shown to remain unchanged. Theoretical docking studies of the triterpene lupeol to beta-CIN provided an explanation for the apparent inability of beta-CIN to bind this ligand, as observed experimentally. 相似文献
94.
Pereira RM Marques CC Baptista MC Vasques MI Horta AE 《Animal reproduction science》2009,111(1):31-40
A positive association between P4 concentration and initial bovine embryo survival has been reported. The objective of this study was to establish two coculture systems as a model to study the influence of progesterone on the initial bovine embryo development. Granulosa cells (GC) or bovine oviduct epithelial cells (BOECs) were used at the base of embryo culture medium microdroplets (TCM199 and 10% of superovulated oestrus cow serum, (SOCS)) supplemented or not with progesterone (P4, 33.4 ng mL(-1)) and/or a progesterone receptor antagonist (onapristone, OP, 2.2x10(-5)M). Presumptive zygotes were transferred to monolayers after in vitro maturation and fertilization of bovine oocytes with thawed swim-up selected sperm. Embryo development was carried out according to the following groups: experiment 1, BOEC (n=378) and BOEC plus OP (n=325); experiment 2, GC (n=514); GC plus OP (n=509); BOEC (n=490); BOEC plus P4 (n=500); BOEC plus P4 and OP (n=502). Embryos were checked for cleavage at day 2 and for stage development between days 8 and 12 of culture. In experiment 1, no differences (P>0.05) were identified between BOEC and BOECOP groups for embryo rates of development, quality or developmental stages. Also in experiment 2, no differences were found in embryo rates of development, quality or developmental stages between embryos cultured under the two coculture systems when no supplementation was added. Embryo development rates were not affected by OP presence in GCOP group. However, P4 negatively affected Day 8 (D8) embryo development rates in BOEC system (BOECP4=16.8+/-2.6% vs. BOEC=23.7+/-1.7%, P=0.02). This negative effect was abolished when P4 antagonist (OP) was added to the culture medium. BOEC supplementation with P4 also induced a delay on embryo development at D8 as confirmed by a lower development score (BOECP4=3.0+/-1.4 vs. GC=3.4+/-0.1, GCOP=3.5+/-0.1, BOEC=3.4+/-0.1 and BOECP4OP=3.5+/-0.1; P<0.05). These results demonstrate that OP supplementation had no harmful effect on embryo development either in granulosa, where P4 is naturally synthesised, or in BOEC coculture systems. Also we can not confirm a direct association between high P4 concentrations and embryo survival during early stages, although P4 may influence early embryo development through different mechanisms mediated by the type of cells present. 相似文献
95.
96.
Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection,an Attenuated Form of HIV Disease
Rita Cavaleiro António P. Baptista Rui S. Soares Rita Tendeiro Russell B. Foxall Perpétua Gomes Rui M. M. Victorino Ana E. Sousa 《PLoS pathogens》2009,5(11)
Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-α production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although having the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4 decline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating pDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the undetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on circulating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC depletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral infection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of IFN-α production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in vitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-α inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-α levels were not elevated in HIV-2 infected individuals. In conclusion, our data in this unique natural model of “attenuated” HIV immunodeficiency contribute to the understanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion of circulating pDC in association with a relatively preserved IFN-α production does occur. 相似文献
97.
98.
Célia Aveleira Áurea Castilho Filipa Baptista Núria Simões Carolina Fernandes Ermelindo Leal António Francisco Ambrósio 《Cytokine》2010,49(3):279-286
Diabetic retinopathy has been considered a low-grade chronic inflammatory disease. The production of interleukin-1β (IL-1β) in the retina is increased, and this finding has been correlated with an increase in blood-retinal barrier permeability, suggesting that IL-1β might have an important role in the pathogenesis of diabetic retinopathy. However, in this context, no attention has been given to interleukin-1 type I receptor (IL-1RI), which is the receptor responsible for IL-1β triggered effects. Therefore, we investigated the effect of high glucose and IL-1β on the IL-1RI regulation in retinal endothelial cells. A time-dependent downregulation of IL-1RI protein levels was detected in retinal endothelial cells exposed (1–24 h) to high glucose, mannitol or IL-1β. Long-term exposure (7 days) to high glucose or mannitol also decreased IL-1RI protein content. IL-1RI downregulation was due to its activation by IL-1β, since it was inhibited by the presence of anti-IL-1RI or anti-IL-1β antibodies. Moreover, IL-1RI downregulation was prevented by lysosome inhibitors, chloroquine and ammonium chloride, but not by proteasome inhibitors, MG132 and lactacystin. We also found that IL-1RI translocates to the nucleus after high glucose or IL-1β treatment. In conclusion, our results indicate that high glucose, probably due to osmotic stress, and IL-1β downregulate IL-1RI in retinal endothelial cells. The downregulation of IL-1RI is triggered by its activation and is due, at least partially, to lysosomal degradation. High glucose and IL-1β also enhance the translocation of IL-1RI to the nucleus. 相似文献
99.
Baptista JC Machado MA Homem RA Torres PS Vojnov AA do Amaral AM 《Genetics and molecular biology》2010,33(1):146-153
The Gram-negative bacterium Xanthomonas axonopodis pv. citri, the causal agent of citrus canker, is a major threat to the citrus industry worldwide. Although this is a leaf spot pathogen, it bears genes highly related to degradation of plant cell walls, which are typically found in plant pathogens that cause symptoms of tissue maceration. Little is known on Xac capacity to cause disease and hydrolyze cellulose. We investigated the contribution of various open reading frames on degradation of a cellulose compound by means of a global mutational assay to selectively screen for a defect in carboxymethyl cellulase (CMCase) secretion in X. axonopodis pv. citri. Screening on CMC agar revealed one mutant clone defective in extracellular glycanase activity, out of nearly 3,000 clones. The insertion was located in the xpsD gene, a component of the type II secretion system (T2SS) showing an influence in the ability of Xac to colonize tissues and hydrolyze cellulose. In summary, these data show for the first time, that X. axonopodis pv. citri is capable of hydrolyzing cellulose in a T2SS-dependent process. Furthermore, it was demonstrated that the ability to degrade cellulose contributes to the infection process as a whole. 相似文献
100.
Elsa Lamy Gonçalo Graça Gonçalo da Costa Catarina Franco Fernando Capela e Silva Elvira Sales Baptista Ana Varela Coelho 《Proteome science》2010,8(1):65