全文获取类型
收费全文 | 298篇 |
免费 | 25篇 |
出版年
2022年 | 3篇 |
2021年 | 11篇 |
2020年 | 11篇 |
2019年 | 4篇 |
2018年 | 14篇 |
2017年 | 6篇 |
2016年 | 17篇 |
2015年 | 26篇 |
2014年 | 22篇 |
2013年 | 33篇 |
2012年 | 27篇 |
2011年 | 27篇 |
2010年 | 11篇 |
2009年 | 13篇 |
2008年 | 10篇 |
2007年 | 11篇 |
2006年 | 19篇 |
2005年 | 14篇 |
2004年 | 9篇 |
2003年 | 6篇 |
2002年 | 12篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1976年 | 1篇 |
1969年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有323条查询结果,搜索用时 296 毫秒
31.
Ana Elisa Böhmer Débora Guerini Souza Gisele Hansel Liz M.B.P. Brum Luis Valmor Portela Diogo Onofre Souza 《Chemico-biological interactions》2010,185(1):53-58
Cyclosporine (CsA) is an immunosuppressive agent frequently used in the clinic for prevention of allograft rejection and for the treatment of autoimmune diseases. Despite its desired action on the immune system, CsA treatment may present serious adverse effects, which are masked by the concomitant use of other drugs. The search for effective immunosuppression protocols which does not affect the quality of life of patients is driving research to investigate the CsA involvement in vascular diseases, frequent in patients under immunosuppression. Thus, 45 non-transplanted Wistar rats were treated for 8 weeks with vehicle or 5 or 15 mg/kg CsA (n = 15/group) by gavage administration to evaluate the specific influence of cyclosporine on the levels of risk factors (metabolic and inflammatory) of vascular disease and its mechanism of action. Therefore, serum insulin levels, glucose tolerance test, serum lipids profile, total homocysteine and fibrinogen levels were assessed. The biochemical alterations reported here suggest the development of a framework straight to diabetes. Glucose homeostasis was affected as indicated by decreased insulin levels and altered glucose tolerance test in CsA 15 mg/kg group compared to other groups. Serum insulin and total homocysteine levels presented a significant negative correlation (R = ? 0.76, P < 0.0001). Fibrinogen and serum lipids profiles were significantly increased in CsA 15 mg/kg group compared to other groups and correlated positively with total homocysteine levels. Considering the well-established correlation among insulin resistance, lipid and total homocysteine levels, hypercoagulability and atherosclerosis, we can assume that this protocol of long-term CsA treatment in non-transplanted rats alter biochemical parameters related to cardiovascular and cerebrovascular risk, mainly in CsA 15 mg/kg group. Insulin and tHcy serum levels appear to be central in this process. 相似文献
32.
Peirano G Souza FS Rodrigues DP;Shigella Study Group 《Memórias do Instituto Oswaldo Cruz》2006,101(3):245-250
A total of 296 Shigella spp. were received from State Public Health Laboratories, during the period from 1999 to 2004, by National Reference Laboratory for Cholera and Enteric Diseases (NRLCED)--IOC/Fiocruz, Rio de Janeiro, Brazil. The frequency of Shigella spp. was: S. flexneri (52.7%), S. sonnei (44.2%), S. boydii (2.3%), and S. dysenteriae (0.6%). The most frequent S. flexneri serovars were 2a and 1b. The highest incidence rates of Shigella isolation were observed in the Southeast (39%) and Northeast (34%) regions and the lowest rate in the South (3%) of Brazil. Strains were further analyzed for antimicrobial susceptibility by disk diffusion method as part of a surveillance program on antimicrobial resistance. The highest rates of antimicrobial resistance were to trimethoprim-sulfamethozaxole (90%), tetracycline (88%), ampicillin (56%), and chloramphenicol (35%). The patterns of antimicrobial resistance among Shigella isolates pose a major difficulty in the determination of an appropriate drug for shigellosis treatment. Continuous monitoring of antimicrobial susceptibilities of Shigella spp. through a surveillance system is thus essential for effective therapy and control measures against shigellosis. 相似文献
33.
GB Menezes FA Pereira CA Duarte TM Carmo HP Silva Filho MA Zarife MA Krieger EA Reis MG Reis 《Memórias do Instituto Oswaldo Cruz》2012,107(5):680-683
The hepatitis C virus (HCV) can be detected in blood and other bodily fluids, such as saliva, semen and gastric juices. The aim of this study was to compare the HCV viral loads in the serum and saliva of infected patients. Twenty-nine patients with detectable HCV RNA in their serum and saliva were included in this study. The HCV viral loads were determined through quantitative real-time polymerase chain reactions. The median viral RNA levels were 5.78 log10 copies in the serum and 3.32 log10 copies in the saliva. We observed that the salivary HCV viral load was significantly lower than the viral load in the serum. Further studies are required to understand the role of saliva in the diagnosis, management and potential transmission of HCV. 相似文献
34.
Fonseca Lde S Vieira GB Sobral LF Ribeiro EO Marsico AG 《Memórias do Instituto Oswaldo Cruz》2012,107(1):142-144
The performance of the nitrate reductase assay (NRA) was compared with the proportion method (PM) on Lowenstein-Jensen medium and the BACTEC MGIT960 assay under routine conditions using 160 clinical isolates of Mycobacterium tuberculosis with a high proportion of resistant strains. The mean time to obtain results was 8.8 days and the overall agreements between NRA and PM and NRA and M960 were 95% and 94%, respectively. NRA was easy to perform and represents a useful tool for the rapid screening of drug-resistant M. tuberculosis strains in low-resource countries. 相似文献
35.
Sharma PP González VL Kawauchi GY Andrade SC Guzmán A Collins TM Glover EA Harper EM Healy JM Mikkelsen PM Taylor JD Bieler R Giribet G 《Molecular phylogenetics and evolution》2012,65(1):64-74
Revived interest in molluscan phylogeny has resulted in a torrent of molecular sequence data from phylogenetic, mitogenomic, and phylogenomic studies. Despite recent progress, basal relationships of the class Bivalvia remain contentious, owing to conflicting morphological and molecular hypotheses. Marked incongruity of phylogenetic signal in datasets heavily represented by nuclear ribosomal genes versus mitochondrial genes has also impeded consensus on the type of molecular data best suited for investigating bivalve relationships. To arbitrate conflicting phylogenetic hypotheses, we evaluated the utility of four nuclear protein-encoding genes-ATP synthase β, elongation factor-1α, myosin heavy chain type II, and RNA polymerase II-for resolving the basal relationships of Bivalvia. We sampled all five major lineages of bivalves (Archiheterodonta, Euheterodonta [including Anomalodesmata], Palaeoheterodonta, Protobranchia, and Pteriomorphia) and inferred relationships using maximum likelihood and Bayesian approaches. To investigate the robustness of the phylogenetic signal embedded in the data, we implemented additional datasets wherein length variability and/or third codon positions were eliminated. Results obtained include (a) the clade (Nuculanida+Opponobranchia), i.e., the traditionally defined Protobranchia; (b) the monophyly of Pteriomorphia; (c) the clade (Archiheterodonta+Palaeoheterodonta); (d) the monophyly of the traditionally defined Euheterodonta (including Anomalodesmata); and (e) the monophyly of Heteroconchia, i.e., (Palaeoheterodonta+Archiheterodonta+Euheterodonta). The stability of the basal tree topology to dataset manipulation is indicative of signal robustness in these four genes. The inferred tree topology corresponds closely to those obtained by datasets dominated by nuclear ribosomal genes (18S rRNA and 28S rRNA), controverting recent taxonomic actions based solely upon mitochondrial gene phylogenies. 相似文献
36.
Kátia Gisele Oliveira Rancura Michelli Rivero Montaño Robson Francisco Carvalho Cesar Martins Adriane Pinto Wasko Luciana Casaletti Alexandre Azevedo 《Acta zoologica》2008,89(1):29-36
This study presents data on myosin Va localization in the central nervous system of rainbow trout. We demonstrate, via immunoblots and immunocytochemistry, the expression of myosin Va in several neuronal populations of forebrain, midbrain, hindbrain and spinal cord. The neuronal populations that express myosin Va in trout constitute a very diverse group that do not seem to have many specific similarities such as neurotransmitters used, cellular size or length of their processes. The intensity of the immunoreactivity and the number of immunoreactive cells differ from region to region. Although there is a broad distribution of myosin Va, it is not present in all neuronal populations. This result is in agreement with a previous report, which indicated that myosin Va is approximately as abundant as conventional myosin II and kinesin, and it is broadly involved in neuronal motility events such as axoplasmatic transport. Furthermore, this distribution pattern is in accordance with what was shown in rats and mice; it indicates phylogenetic maintenance of the myosin Va main functions. 相似文献
37.
Graziele Fonseca de Sousa Maira de Assis Lima Débora Fernandes Custodio Vanessa Morais Freitas Gisele Monteiro 《PloS one》2015,10(12)
The use of carboplatin in cancer chemotherapy is limited by the emergence of drug resistance. To understand the molecular basis for this resistance, a chemogenomic screen was performed in 53 yeast mutants that had previously presented strong sensitivity to this widely used anticancer agent. Thirty-four mutants were responsive to carboplatin, and from these, 21 genes were selected for further studies because they have human homologues. Sixty percent of these yeast genes possessed human homologues which encoded proteins that interact with cullin scaffolds of ubiquitin ligases, or whose mRNA are under the regulation of Human antigen R (HuR) protein. Both HuR and cullin proteins are regulated through NEDDylation post-translational modification, and so our results indicate that inhibition of this process should sensitise resistant tumour cells to carboplatin. We showed that treatment of a tumour cell line with MLN4924, a NEDDylation inhibitor, overcame the resistance to carboplatin. Our data suggest that inhibition of NEDDylation may be a useful strategy to resensitise tumour cells in patients that have acquired carboplatin resistance. 相似文献
38.
Pedro Gnaspini Gisele C. S. Rodrigues 《Journal of Zoological Systematics and Evolutionary Research》2011,49(4):273-284
Arachnids of the order Opiliones (harvestmen), which includes around 6000 specìes, have a pair of scent glands that open at the sides of the body, producing substances used as defence. Several types of behavioural, morphological and chemical defensive mechanisms have been identified in the order as a whole, although some of these tactics were restricted to particular groups. Only around 60 species have been studied from this perspective so far, more than half of which belong to the largest harvestman family within the order Laniatores, the Gonyleptidae, and have only recently been studied in an evolutionary perspective, showing the usefulness of defensive characters in taxonomy and evolutionary biology. Within Laniatores, the Grassatores clade includes the Gonyleptidae and 20 additional families, mostly poorly or not previously studied. We describe the morphology of the structures involved in fluid displacement during chemical defence in 15 of these families (data on two additional families are available from the literature) and discuss the evolution of such traits based on an available phylogenetic hypothesis of relationships within Grassatores, using the representatives of Triaenonychidae (a non‐Grassatores family of Laniatores) for comparison. We conclude that most non‐gonyleptoid Grassatores share (maybe plesiomorphically) a series of characteristics, mostly strongly different from what is observed within the gonyleptoids, and that smaller groups seem to share diagnostic features related to chemical defence, as is the case of stygnids, cosmetids and triaenonychines, and especially of manaosbiids and cranaids, whose defensive morphologies largely resemble those of derived gonyleptids. The following main synapomorphies were detected: (a) Grassatores: the presence of a deep and well‐defined descending channel; (b) Samooidea+Zalmoxoidea+Assamioidea+Gonyleptoidea: lateral pegs along the lateral channel; (c) Samooidea+Zalmoxoidea: deep channels forming an H on the dorsal scute; (d) Gonyleptoidea: ozopore cutting dorsally (reversing in Agoristenidae and Stygnidae to a laterally placed oval ozopore), a wide and smooth lateral channel, reversing to a lateral channel whose bottom is covered with either small plates (Agoristenidae) or high tubercles (Stygnidae), and apophyses of coxa II close to or covering the ozopore. 相似文献
39.
Chemically-defined medium for growth and differentiation of mixed epithelial and connective tissues in organ culture 总被引:1,自引:0,他引:1
Gisele M. Hodges Anthony H. Melcher 《In vitro cellular & developmental biology. Plant》1976,12(6):450-459
The effect on tissue differentiation and growth in vitro of certain of the factors implicated in collagen synthesis (ascorbic
acid, α-ketoglutarate and oxygen) and the influence of hydrocortisone was studied using organ cultures of fetal mouse mandible
as a mixed epithelial and connective tissue system. Using serum-free Waymouth’s MB 752/1 chemically-defined medium, addition
of high levels of ascorbic acid (300 μg per ml), hydrocortisone (1 μg per ml) and oxygen (95%) enhanced differentiation in
a number of tissues, in particular skin and appendages, tooth germs and bone, while osteoid and dentine production were noticeably
promoted. It is suggested that an essential aspect of media design for organ culture involves the incorporation of collagen-promoting
factors to the in vitro environment particularly with regard to the controlling role implicated for collagen in a variety
of biological processes.
Some of the work reported here was undertaken while A. H. Melcher was a member of the Department of Dental Science, Royal
College of Surgeons of England, London, England. 相似文献
40.
Danilo E. F. L. Fl?res Barbara M. Tomotani Patricia Tachinardi Gisele A. Oda Veronica S. Valentinuzzi 《PloS one》2013,8(7)
Subterranean rodents spend most of the day inside underground tunnels, where there is little daily change in environmental variables. Our observations of tuco-tucos (Ctenomys aff. knighti) in a field enclosure indicated that these animals perceive the aboveground light-dark cycle by several bouts of light-exposure at irregular times during the light hours of the day. To assess whether such light-dark pattern acts as an entraining agent of the circadian clock, we first constructed in laboratory the Phase Response Curve for 1 h light-pulses (1000lux). Its shape is qualitatively similar to other curves reported in the literature and to our knowledge it is the first Phase Response Curve of a subterranean rodent. Computer simulations were performed with a non-linear limit-cycle oscillator subjected to a simple model of the light regimen experienced by tuco-tucos. Results showed that synchronization is achieved even by a simple regimen of a single daily light pulse scattered uniformly along the light hours of the day. Natural entrainment studies benefit from integrated laboratory, field and computational approaches. 相似文献