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排序方式: 共有63条查询结果,搜索用时 151 毫秒
21.
22.
Yihong Xie Yi Tan Virasakdi Chongsuvivatwong Xinghua Wu Fuyin Bi Stephen C. Hadler Chuleeporn Jiraphongsa Vorasith Sornsrivichai Mei Lin Yi Quan 《PloS one》2015,10(12)
Objectives
Acute meningitis and encephalitis (AME) are common diseases with the main pathogens being viruses and bacteria. As specific treatments are different, it is important to develop clinical prediction rules to distinguish aseptic from bacterial or fungal infection. In this study we evaluated the incidence rates, seasonal variety and the main etiologic agents of AME, and identified factors that could be used to predict the etiologic agents.Methods
A population-based AME syndrome surveillance system was set up in Guigang City, Guangxi, involving 12 hospitals serving the study communities. All patients meeting the case definition were investigated. Blood and/or cerebrospinal fluid were tested for bacterial pathogens using culture or RT-PCR and serological tests for viruses using enzyme-linked immunosorbent assays. Laboratory testing variables were grouped using factor analysis. Multinomial logistic regression was used to predict the etiology of AME.Results
From May 2007 to June 2012, the annual incidence rate of AME syndrome, and disease specifically caused by Japanese encephalitis (JE), other viruses, bacteria and fungi were 12.55, 0.58, 4.57, 0.45 and 0.14 per 100,000 population, respectively. The top three identified viral etiologic agents were enterovirus, mumps virus, and JE virus, and for bacteria/fungi were Streptococcus sp., Cryptococcus neoformans and Staphylococcus sp. The incidence of JE and other viruses affected younger populations and peaked from April to August. Alteration of consciousness and leukocytosis were more likely to be caused by JE, bacteria and fungi whereas CSF inflammation was associated with bacterial/fungal infection.Conclusions
With limited predictive validity of symptoms and signs and routine laboratory tests, specific tests for JE virus, mumps virus and enteroviruses are required to evaluate the immunization impact and plan for further intervention. CSF bacterial culture cannot be omitted in guiding clinical decisions regarding patient treatment. 相似文献23.
Sarah J. Smith Annelise Casellato Kieran S. Hadler Nataša Mitić Mark J. Riley Adailton J. Bortoluzzi Bruno Szpoganicz Gerhard Schenk Ademir Neves Lawrence R. Gahan 《Journal of biological inorganic chemistry》2007,12(8):1207-1220
Purple acid phosphatase from pig uterine fluid (uteroferrin), a representative of the diverse family of binuclear metallohydrolases, requires a heterovalent Fe(III)Fe(II) center for catalytic activity. The active-site structure and reaction mechanism of this enzyme were probed with a combination of methods including metal ion replacement and biomimetic studies. Specifically, the asymmetric ligand 2-bis{[(2-pyridylmethyl)-aminomethyl]-6-[(2-hydroxybenzyl)(2-pyridylmethyl)]aminomethyl}-4-methylphenol and two symmetric analogues that contain the softer and harder sites of the asymmetric unit were employed to assess the site selectivity of the trivalent and divalent metal ions using (71)Ga NMR, mass spectrometry and X-ray crystallography. An exclusive preference of the harder site of the asymmetric ligand for the trivalent metal ion was observed. Comparison of the reactivities of the biomimetics with Ga(III)Zn(II) and Fe(III)Zn(II) centers indicates a higher turnover for the former, suggesting that the M(III)-bound hydroxide acts as the reaction-initiating nucleophile. Catalytically active Ga(III)Zn(II) and Fe(III)Zn(II) derivatives were also generated in the active site of uteroferrin. As in the case of the biomimetics, the Ga(III) derivative has increased reactivity, and a comparison of the pH dependence of the catalytic parameters of native uteroferrin and its metal ion derivatives supports a flexible mechanistic strategy whereby both the mu-(hydr)oxide and the terminal M(III)-bound hydroxide can act as nucleophiles, depending on the metal ion composition, the geometry of the second coordination sphere and the substrate. 相似文献
24.
Kan NG Stemmler MP Junghans D Kanzler B de Vries WN Dominis M Kemler R 《Development (Cambridge, England)》2007,134(1):31-41
During mammalian embryogenesis the trophectoderm represents the first epithelial structure formed. The cell adhesion molecule E-cadherin is ultimately necessary for the transition from compacted morula to the formation of the blastocyst to ensure correct establishment of adhesion junctions in the trophectoderm. Here, we analyzed to what extent E-cadherin confers unique adhesion and signaling properties in trophectoderm formation in vivo. Using a gene replacement approach, we introduced N-cadherin cDNA into the E-cadherin genomic locus. We show that the expression of N-cadherin driven from the E-cadherin locus reflects the expression pattern of endogenous E-cadherin. Heterozygous mice co-expressing E- and N-cadherin are vital and show normal embryonic development. Interestingly, N-cadherin homozygous mutant embryos phenocopy E-cadherin-null mutant embryos. Upon removal of the maternal E-cadherin, we demonstrate that N-cadherin is able to provide sufficient cellular adhesion to mediate morula compaction, but is insufficient for the subsequent formation of a fully polarized functional trophectoderm. When ES cells were isolated from N-cadherin homozygous mutant embryos and teratomas were produced, these ES cells differentiated into a large variety of tissue-like structures. Importantly, different epithelial-like structures expressing N-cadherin were formed, including respiratory epithelia, squamous epithelia with signs of keratinization and secretory epithelia with goblet cells. Thus, N-cadherin can maintain epithelia in differentiating ES cells, but not during the formation of the trophectoderm. Our results point to a specific and unique function for E-cadherin during mouse preimplantation development. 相似文献
25.
X Zhu RT Libby WN de Vries RS Smith DL Wright RT Bronson KL Seburn SW John 《PLoS genetics》2012,8(8):e1002853
Neuronal loss and axonal degeneration are important pathological features of many neurodegenerative diseases. The molecular mechanisms underlying the majority of axonal degeneration conditions remain unknown. To better understand axonal degeneration, we studied a mouse mutant wabbler-lethal (wl). Wabbler-lethal (wl) mutant mice develop progressive ataxia with pronounced neurodegeneration in the central and peripheral nervous system. Previous studies have led to a debate as to whether myelinopathy or axonopathy is the primary cause of neurodegeneration observed in wl mice. Here we provide clear evidence that wabbler-lethal mutants develop an axonopathy, and that this axonopathy is modulated by Wld(s) and Bax mutations. In addition, we have identified the gene harboring the disease-causing mutations as Atp8a2. We studied three wl alleles and found that all result from mutations in the Atp8a2 gene. Our analysis shows that ATP8A2 possesses phosphatidylserine translocase activity and is involved in localization of phosphatidylserine to the inner leaflet of the plasma membrane. Atp8a2 is widely expressed in the brain, spinal cord, and retina. We assessed two of the mutant alleles of Atp8a2 and found they are both nonfunctional for the phosphatidylserine translocase activity. Thus, our data demonstrate for the first time that mutation of a mammalian phosphatidylserine translocase causes axon degeneration and neurodegenerative disease. 相似文献
26.
Epidemiological and clinical features of 1,149 persons with Lyme disease identified by laboratory-based surveillance in Connecticut 总被引:2,自引:0,他引:2
L R Petersen A H Sweeney P J Checko L A Magnarelli P A Mshar R A Gunn J L Hadler 《The Yale journal of biology and medicine》1989,62(3):253-262
Laboratory-based surveillance of Lyme disease in Connecticut during 1984 and 1985 identified 3,098 persons with suspected Lyme disease; 1,149 were defined as cases. Lyme disease incidence in Connecticut towns ranged from none to 1,407 cases per 100,000 population in 1985. A comparison of 1985 data with data from 1977 epidemiologic studies indicated that incidence increased by 129 percent to 453 percent in towns previously known to be endemic for Lyme disease and that Lyme disease had spread northward into towns thought to be free of Lyme disease in 1977. Children aged five to 14 years had the highest incidence. Of persons with Lyme disease, 83 percent had erythema migrans, 24 percent had arthritis, 8 percent had neurologic sequelae, and 2 percent had cardiac sequelae. The distribution of symptoms was age-dependent: case-persons less than 20 years old were almost twice as likely to have arthritis than older case-persons (35 percent versus 18 percent). Of persons with arthritis, 92 percent of those less than 20 years of age, compared to 68 percent of older persons, did not have antecedent erythema migrans. We conclude that Lyme disease is increasing in incidence and geographic distribution in Connecticut. Of those with Lyme disease, children may be more likely than adults to develop arthritis and have it as their first major disease manifestation. 相似文献
27.
De Keersmaecker K Real PJ Gatta GD Palomero T Sulis ML Tosello V Van Vlierberghe P Barnes K Castillo M Sole X Hadler M Lenz J Aplan PD Kelliher M Kee BL Pandolfi PP Kappes D Gounari F Petrie H Van der Meulen J Speleman F Paietta E Racevskis J Wiernik PH Rowe JM Soulier J Avran D Cavé H Dastugue N Raimondi S Meijerink JP Cordon-Cardo C Califano A Ferrando AA 《Nature medicine》2010,16(11):1321-1327
28.
Natalia V. Varlakhanova Rebecca F. Cotterman Wilhelmine N. deVries Judy Morgan Leah Rae Donahue Stephen Murray Barbara B. Knowles Paul S. Knoepfler 《Differentiation; research in biological diversity》2010
While endogenous Myc (c-myc) and Mycn (N-myc) have been reported to be separately dispensable for murine embryonic stem cell (mESC) function, myc greatly enhances induced pluripotent stem (iPS) cell formation and overexpressed c-myc confers LIF-independence upon mESC. To address the role of myc genes in ESC and in pluripotency generally, we conditionally knocked out both c- and N-myc using myc doubly homozygously floxed mESC lines (cDKO). Both lines of myc cDKO mESC exhibited severely disrupted self-renewal, pluripotency, and survival along with enhanced differentiation. Chimeric embryos injected with DKO mESC most often completely failed to develop or in rare cases survived but with severe defects. The essential nature of myc for self-renewal and pluripotency is at least in part mediated through orchestrating pluripotency-related cell cycle and metabolic programs. This study demonstrates that endogenous myc genes are essential for mESC pluripotency and self-renewal as well as providing the first evidence that myc genes are required for early embryogenesis, suggesting potential mechanisms of myc contribution to iPS cell formation. 相似文献
29.
Fernanda Ely Kieran S. Hadler Nataša Mitić Lawrence R. Gahan David L. Ollis Nicholas M. Plugis Marie T. Russo James A. Larrabee Gerhard Schenk 《Journal of biological inorganic chemistry》2011,16(5):777-787
The organophosphate-degrading enzyme from Agrobacterium radiobacter (OpdA) is a highly efficient catalyst for the degradation of pesticides and some nerve agents such as sarin. OpdA requires
two metal ions for catalytic activity, and hydrolysis is initiated by a nucleophilic hydroxide that is bound to one of these
metal ions. The precise location of this nucleophile has been contentious, with both a terminal and a metal-ion-bridging hydroxide
as likely candidates. Here, we employed magnetic circular dichroism to probe the electronic and geometric structures of the
Co(II)-reconstituted dinuclear metal center in OpdA. In the resting state the metal ion in the more secluded α site is five-coordinate,
whereas the Co(II) in the solvent-exposed β site is predominantly six-coordinate with two terminal water ligands. Addition
of the slow substrate diethyl 4-methoxyphenyl phosphate does not affect the α site greatly but lowers the coordination number
of the β site to five. A reduction in the exchange coupling constant indicates that substrate binding also triggers a shift
of the μ-hydroxide into a pseudoterminal position in the coordination sphere of either the α or the β metal ion. Mechanistic
implications of these observations are discussed. 相似文献
30.
Duncan EL Danoy P Kemp JP Leo PJ McCloskey E Nicholson GC Eastell R Prince RL Eisman JA Jones G Sambrook PN Reid IR Dennison EM Wark J Richards JB Uitterlinden AG Spector TD Esapa C Cox RD Brown SD Thakker RV Addison KA Bradbury LA Center JR Cooper C Cremin C Estrada K Felsenberg D Glüer CC Hadler J Henry MJ Hofman A Kotowicz MA Makovey J Nguyen SC Nguyen TV Pasco JA Pryce K Reid DM Rivadeneira F Roux C Stefansson K Styrkarsdottir U Thorleifsson G Tichawangana R Evans DM Brown MA 《PLoS genetics》2011,7(4):e1001372
Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. 相似文献