全文获取类型
收费全文 | 106篇 |
免费 | 3篇 |
专业分类
109篇 |
出版年
2021年 | 4篇 |
2019年 | 1篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 9篇 |
2011年 | 5篇 |
2010年 | 9篇 |
2009年 | 5篇 |
2008年 | 5篇 |
2007年 | 7篇 |
2006年 | 4篇 |
2005年 | 2篇 |
2004年 | 5篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2001年 | 1篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1988年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有109条查询结果,搜索用时 0 毫秒
71.
72.
Víctor de Carvalho Martins Liliana Princisval França Yasmim da Silva Ferreira Daniele Cabral Pires Bárbara de Souza Cardoso Manuela Cristina Pessanha de Araújo Santiago Sidney Pacheco Marcelo da Costa Souza Cristiano Jorge Riger Ronoel Luiz de Oliveira Godoy Mario Geraldo de Carvalho 《化学与生物多样性》2021,18(6):e2100054
Eugenia copacabanensis and Myrciaria tenella are present in restingas of the Atlantic Forest, but little information is available about their chemical and biological potential. In this context, the hexane, dichloromethane, ethyl acetate and butanol fractions from the leaves of methanolic extract were analyzed by GC/MS and HPLC-DAD and the antioxidant potential was determined by DPPH and ABTS assays and using a Saccharomyces cerevisiae model. Dereplication allowed the identification of 68 compounds, 42 and 41 of which, respectively, are first reported here for E. copacabanensis and M. tenella. In vivo results revealed that the ethyl acetate and butanol fractions showed expressive antioxidant protection in the BY4741 and Δgsh1 strains, with greater impact on glutathione-deficient cells. With a high diversity of phenolic compounds, these polar fractions of E. copacabanensis and M. tenella leaves are potential protectors against intracellular oxidative stress. 相似文献
73.
Molecular evolution of the Sex-Ratio inversion complex in Drosophila pseudoobscura: analysis of the Esterase-5 gene region 总被引:2,自引:0,他引:2
The Sex-Ratio chromosome in Drosophila pseudoobscura is subject to meiotic
drive. It is associated with a series of three nonoverlapping paracentric
inversions on the right arm of the X chromosome. The esterase-5 gene region
has been localized to section 23 within the subbasal inversion of the
Sex-Ratio inversion complex, making esterase- 5 a convenient locus for
molecular evolutionary analyses of the Sex- Ratio inversion complex and the
associated drive system. A 504-bp fragment of noncoding, intergenic DNA
from the esterase-5 gene region was amplified and sequenced from 14
Sex-Ratio and 14 Standard X chromosomes of D. pseudoobscura, and from 9 X
chromosomes of its two sibling species, Drosophila persimilis and
Drosophila miranda. There is extensive sequence differentiation between the
Sex-Ratio and Standard chromosomal types. The common Standard chromosome is
highly polymorphic, while, as expected from either the neutral mutation
theory or the selective sweep hypothesis, the rarer Sex-Ratio chromosome
has much less within-chromosome nucleotide polymorphism. We estimate that
the Standard and Sex-Ratio chromosomes in D. pseudoobscura diverged between
700,000 and 1.3 Mya, or at least 2 million generations ago. The clustering
of D. pseudoobscura Sex-Ratio chromosomes in a neighbor- joining phylogeny
indicates a fairly old, monophyletic origin in this species. It appears
from these data that Sex-Ratio genes were present prior to the divergence
of D. pseudoobscura and D. persimilis and that both the Standard and
Sex-Ratio chromosomes of D. persimilis were derived from the Standard
chromosome of D. pseudoobscura after the inversion events that isolated the
D. pseudoobscura Sex-Ratio chromosome.
相似文献
74.
Monica L Andersen Raquel CS Martins Tathiana AF Alvarenga Isabela B Antunes Ligia A Papale Sergio Tufik 《Reproductive biology and endocrinology : RB&E》2007,5(1):7
Background
Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. 相似文献75.
A C Reis A L Alessandri R M Athayde D A Perez J P Vago T V ávila T P T Ferreira A CS de Arantes D de Sá Coutinho M A Rachid L P Sousa M A Martins G B Menezes A G Rossi M M Teixeira V Pinho 《Cell death & disease》2015,6(2):e1632
Eosinophils are effector cells that have an important role in the pathogenesis of allergic disease. Defective removal of these cells likely leads to chronic inflammatory diseases such as asthma. Thus, there is great interest in understanding the mechanisms responsible for the elimination of eosinophils from inflammatory sites. Previous studies have demonstrated a role for certain mediators and molecular pathways responsible for the survival and death of leukocytes at sites of inflammation. Reactive oxygen species have been described as proinflammatory mediators but their role in the resolution phase of inflammation is poorly understood. The aim of this study was to investigate the effect of reactive oxygen species in the resolution of allergic inflammatory responses. An eosinophilic cell line (Eol-1) was treated with hydrogen peroxide and apoptosis was measured. Allergic inflammation was induced in ovalbumin sensitized and challenged mouse models and reactive oxygen species were administered at the peak of inflammatory cell infiltrate. Inflammatory cell numbers, cytokine and chemokine levels, mucus production, inflammatory cell apoptosis and peribronchiolar matrix deposition was quantified in the lungs. Resistance and elastance were measured at baseline and after aerosolized methacholine. Hydrogen peroxide accelerates resolution of airway inflammation by induction of caspase-dependent apoptosis of eosinophils and decrease remodeling, mucus deposition, inflammatory cytokine production and airway hyperreactivity. Moreover, the inhibition of reactive oxygen species production by apocynin or in gp91phox−/− mice prolonged the inflammatory response. Hydrogen peroxide induces Eol-1 apoptosis in vitro and enhances the resolution of inflammation and improves lung function in vivo by inducing caspase-dependent apoptosis of eosinophils.Eosinophils express numerous receptors and secrete a wide variety of inflammatory mediators that influence many innate and adaptive immune responses. These multifunctional cells are important in the defense against helminth infection and are involved in the pathogenesis of many eosinophilic dominant allergic diseases.1 High levels of eosinophil granule proteins (such as major basic protein (MBP)) have been found in bronchoalveolar lavage fluid from patients with asthma and evidence indicates that high-concentration granule products have contributed to the development of airway hyperreactivity (AHR), a cardinal feature of asthma.2 Asthma is an inflammatory disease of the airways with participation of many cell types including leukocytes especially eosinophils and lymphocytes.3, 4 Activation of these cells (mainly lymphocytes) leads to the release of proinflammatory mediators and cytokines such as leukotriene B4, interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-9 (IL-9), interleukin-13 (IL-13) and colony-stimulating factor granulocyte-macrophage (GM-CSF).3, 5, 6, 7 Investigations using preclinical animal models of asthma and clinical studies in patients with asthma have demonstrated that the presence of eosinophils in the lungs are associated with epithelial damage, goblet cell hyperplasia, smooth muscle hypertrophy and airway hyperresponsiveness resulting in airflow limitation which can be fatal.3, 8, 9, 10 Recently, anti-IL-5 treatment has been shown to ameliorate lung function in patients with eosinophilic asthma.11Apoptosis of leukocytes is regarded as an important process for the successful resolution of inflammatory responses. Reduced eosinophil apoptosis in bronchoalveolar lavage (BAL) fluid has been shown to correlate positively with severity of asthma.3, 12, 13, 14 Indeed, defective leukocyte apoptosis and subsequent removal of apoptotic cells by phagocytes is thought to be important for the initiation and propagation of chronic inflammatory diseases such as asthma.15 Therefore, a balance in the tissue microenvironment between pro- and antiapoptotic signals is likely to greatly influence the load of eosinophils in the asthmatic lung.16 Thus, there is a great interest in understanding the mechanisms responsible for the elimination of eosinophils and other leukocytes and inactivation of proinflammatory mediators in inflammatory sites.17Several molecular pathways have been shown to modulate the survival and death of leukocytes at sites of inflammation, including reactive oxygen species (ROS).18 ROS are a family of molecules containing oxygen and includes hydrogen peroxide (H2O2), superoxide O2−, hydroxyl radical (OH) and nitric oxide (NO).19 In inflammatory conditions, ROS are increased as they help in neutralizing invading organisms during infection either directly or indirectly by formation of extracellular traps (ETs).20 ROS have traditionally been regarded as quintessentially proinflammatory. However, evidence for ROS-mediated anti-inflammatory actions has been described.21 The importance for ROS production in the context of infection can be exemplified in patients with chronic granulomatous disease (CGD) where defective production in ROS results in multiple infections and often early death.22, 23 Furthermore, studies in mouse models have shown that NADPH oxidase is key for regulating lung inflammation and injury as well as NF-κB activation and downstream cytokine production in response to LPS.24 More recently, our group has demonstrated that NADPH oxidase-derived H2O2 is directly linked to induction of apoptosis of neutrophils and resolution of inflammation in a model of antigen-induced arthritis.18 However, the role of ROS in the context of the resolution of allergic inflammation is still unknown.Here, we evaluated whether H2O2 drives apoptosis of eosinophils and thereby influences the resolution of established eosinophilic inflammation and reduction of airflow obstruction. Our study provides evidence that H2O2 is released during allergic inflammation in a gp91phox−/−-dependent manner and induces a caspase-dependent proapoptotic effect in eosinophils, thus having a crucial role in the resolution of allergic inflammation. 相似文献
76.
Raimundo Fernandes de Araújo Júnior Ana Luiza CS Leit?o Oliveira Raniere Fagundes de Melo Silveira Hugo Alexandre de Oliveira Rocha Pedro de Fran?a Cavalcanti Aurigena Antunes de Araújo 《Experimental biology and medicine (Maywood, N.J.)》2015,240(1):34-44
It has been well-characterized that the renin-angiotensin system (RAS) physiologically regulates systemic arterial pressure. However, RAS signaling has also been shown to increase cell proliferation during malignancy, and angiotensin receptor blockers (ARBs) are able to decrease pro-survival signaling by inhibiting anti-apoptotic molecules and suppressing caspase activity. In this study, the apoptotic effects of telmisartan, a type of ARB, was evaluated using a non-cancerous human renal cell line (HEK) and a human renal cell carcinoma (RCC) cell line (786). Both types of cells were treated with telmisartan for 4 h, 24 h, and 48 h, and then were assayed for levels of apoptosis, caspase-3, and Bcl-2 using MTT assays, flow cytometry, and immunostaining studies. Analysis of variance was used to identify significant differences between these data (P < 0.05). Following the treatment of 786 cells with 100 µM and 200 µM telmisartan, a marked inhibition of cell proliferation was observed. 50 µM cisplatin also caused high inhibition of these cells. Moreover, these inhibitions were both concentration- and time-dependent (P < 0.05). Various apoptotic effects were also observed compared with control cells at the 24 h and 48 h timepoints assayed (P < 0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2 were detected, consistent with induction of cell death. In contrast, treatment of HEK cells with telmisartan did not produce an apoptotic effect compared with control cells at the 24 h timepoint (P > 0.05). Treatment with cisplatin promoted in HEK cells high index of apoptosis (P < 0.001). Taken together, these results suggest that telmisartan induces apoptosis via down-regulation of Bcl-2 and involvement of caspase-3 in human RCC cells. 相似文献
77.
ZOLTÁN ÁCS GEORGE MELIKA ZSOLT PÉNZES JULI PUJADE-VILLAR GRAHAM N. STONE 《Systematic Entomology》2007,32(1):70-80
Abstract Oak gallwasps (Hymenoptera; Cynipidae, tribe Cynipini) are cyclically parthenogenetic insects that induce galls on specific plant hosts in the family Fagaceae. Understanding the processes underlying the evolution of specific oak associations requires knowledge of the phylogenetic relationships among oak gallwasp genera. Although three major lineages of oak gallwasps have been identified, the status and relationships of several species‐poor but biologically significant genera remain unresolved. Two such genera are Chilaspis and Dryocosmus, whose western palaearctic species all gall oaks in the section Cerris. Dryocosmus is particularly significant biologically because it includes: (a) the only palaearctic gallwasp to gall chestnuts, Castanea, and (b) nearctic species. The oak section Cerris is wholly absent from the nearctic, and the relationship between palaearctic and nearctic Dryocosmus is significant for patterns of host plant evolution in the tribe as a whole. We examined the relationships between Chilaspis, Dryocosmus and other oak cynipid genera using cladograms from sequence data for two mitochondrial loci (cytochrome c oxidase subunit I and cytochrome b) and two nuclear loci (the 28S ribosomal gene regions D2 and D3–5). Our analyses support the following conclusions: (1) palaearctic Chilaspis and Dryocosmus species form an intermingled monophyletic group. (2) We propose that Chilaspis Mayr, 1881 is a syn.n. of Dryocosmus Giraud, 1859 and propose the name D. mayri as a comb.rev. for the species previously named C. mayri, and D. nitidus and D. israeli as comb.n. of C. nitida and C. israeli, respectively. (3) We reassess the utility of morphological characters previously regarded as diagnostic for these genera. (4) Two species previously known only from a single generation represent two halves of a single species lifecycle. Dryocosmus nervosus is here designated a syn.n. of D. cerriphilus. (5) The nearctic species D. favus lies outside the palaearctic Chilaspis/Dryocosmus clade, and Dryocosmus as currently recognized is not a monophyletic group. (6) Dryocosmus/Chilaspis is closely related to the other oak gallwasp taxa (Aphelonyx, Plagiotrochus, Pseudoneuroterus, Trichagalma, and some Neuroterus species) galling section Cerris oaks. This implies an early branching evolution of this oak association within this group, and supports previous work showing the rarity of oak gallwasp host shifts. 相似文献
78.
Umesh CS Yadav Leopoldo Aguilera-Aguirre Istvan Boldogh Kota V Ramana Satish K Srivastava 《Respiratory research》2011,12(1):145
Background
Childhood hospitalization related to asthma remains at historically high levels, and its incidence is on the rise world-wide. Previously, we have demonstrated that aldose reductase (AR), a regulatory enzyme of polyol pathway, is a major mediator of allergen-induced asthma pathogenesis in mouse models. Here, using AR null (AR-/-) mice we have investigated the effect of AR deficiency on the pathogenesis of ragweed pollen extract (RWE)-induced allergic asthma in mice and also examined the efficacy of enteral administration of highly specific AR inhibitor, fidarestat.Methods
The wild type (WT) and AR-/- mice were sensitized and challenged with RWE to induce allergic asthma. AR inhibitor, fidarestat was administered orally. Airway hyper-responsiveness was measured in unrestrained animals using whole body plethysmography. Mucin levels and Th2 cytokine in broncho-alveolar lavage (BAL) were determined using mouse anti-Muc5A/C ELISA kit and multiplex cytokine array, respectively. Eosinophils infiltration and goblet cells were assessed by H&E and periodic acid Schiff (PAS)-staining of formalin-fixed, paraffin-embedded lung sections. T regulatory cells were assessed in spleen derived CD4+CD25+ T cells population.Results
Deficiency of AR in mice led to significantly decreased PENH, a marker of airway hyper-responsiveness, metaplasia of airway epithelial cells and mucus hyper-secretion following RWE-challenge. This was accompanied by a dramatic decrease in infiltration of eosinophils into sub-epithelium of lung as well as in BAL and release of Th2 cytokines in response to RWE-challenge of AR-/- mice. Further, enteral administration of fidarestat significantly prevented eosinophils infiltration, airway hyper-responsiveness and also markedly increased population of T regulatory (CD4+CD25+FoxP3+) cells as compared to RWE-sensitized and challenged mice not treated with fidarestat.Conclusion
Our results using AR-/- mice strongly suggest the role of AR in allergic asthma pathogenesis and effectiveness of oral administration of AR inhibitor in RWE-induced asthma in mice supports the use of AR inhibitors in the treatment of allergic asthma. 相似文献79.
Introduction
Traumatic joint injury damages cartilage and causes adjacent joint tissues to release inflammatory cytokines, increasing the risk of developing osteoarthritis. The main objective of this study was to determine whether the combined catabolic effects of mechanical injury, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) on cartilage could be abolished by short-term treatment with glucocorticoids such as dexamethasone. 相似文献80.
Shui-Lian Yu Paul KS Chan Chun-Kwok Wong Cheuk-Chun Szeto Suzanne C Ho Karine So May MY Yu So-Fan Yim Tak-Hong Cheung Martin CS Wong Jo LK Cheung Apple CM Yeung Edmund K Li Lai-Shan Tam 《Arthritis research & therapy》2012,14(2):R80
IntroductionPrevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) infection. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence.MethodsProtein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA.ResultsFor subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone; while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells.ConclusionsIn conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response. 相似文献