全文获取类型
收费全文 | 93篇 |
免费 | 4篇 |
专业分类
97篇 |
出版年
2022年 | 2篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 2篇 |
2014年 | 4篇 |
2013年 | 4篇 |
2012年 | 6篇 |
2011年 | 5篇 |
2010年 | 4篇 |
2009年 | 5篇 |
2007年 | 4篇 |
2006年 | 3篇 |
2005年 | 3篇 |
2004年 | 4篇 |
2003年 | 1篇 |
2002年 | 6篇 |
2001年 | 3篇 |
1999年 | 1篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1992年 | 2篇 |
1990年 | 3篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1969年 | 2篇 |
排序方式: 共有97条查询结果,搜索用时 12 毫秒
11.
Clustered regularly interspaced short palindromic repeats (CRISPR) are currently a topic of interest in microbiology due to their role as a prokaryotic immune system. Investigations of CRISPR distribution and characterization to date have focused on pathogenic bacteria, while less is known about CRISPR in commensal bacteria, where they may have a significant role in the ecology of the microbiota of humans and other animals, and act as a recorder of interactions between bacteria and viruses. A combination of PCR and sequencing was used to determine prevalence and distribution of CRISPR arrays in Enterococcus faecalis and Enterococcus hirae isolates from the feces of healthy pigs. Both type II CRISPR–Cas and Orphan CRISPR (without Cas genes) were detected in the 195 isolates examined. CRISPR–Cas was detected in 52 (46/88) and 42 % (45/107) E. faecalis and E. hirae isolates, respectively. The prevalence of Orphan CRISPR arrays was higher in E. faecalis isolates (95 %, 84/88) compared with E. hirae isolates (49 %, 53/107). Species-specific repeat sequences were identified in Orphan CRISPR arrays, and 42 unique spacer sequences were identified. Only two spacers matched previously characterized pig virome sequences, and many were apparently derived from chromosomal sequences of enterococci. Surprisingly, 17 (40 %) of the spacers were detected in both species. Shared spacer sequences are evidence of a lack of species specificity in the agents and mechanisms responsible for integration of spacers, and the abundance of spacer sequences corresponding to bacterial chromosomal sequences reflects interspecific interactions within the intestinal microbiota. 相似文献
12.
Katyal S el-Khamisy SF Russell HR Li Y Ju L Caldecott KW McKinnon PJ 《The EMBO journal》2007,26(22):4720-4731
Defective Tyrosyl-DNA phosphodiesterase 1 (TDP1) can cause spinocerebellar ataxia with axonal neuropathy (SCAN1), a neurodegenerative syndrome associated with marked cerebellar atrophy and peripheral neuropathy. Although SCAN1 lymphoblastoid cells show pronounced defects in the repair of chromosomal single-strand breaks (SSBs), it is unknown if this DNA repair activity is important for neurons or for preventing neurodegeneration. Therefore, we generated Tdp1-/- mice to assess the role of Tdp1 in the nervous system. Using both in vitro and in vivo assays, we found that cerebellar neurons or primary astrocytes derived from Tdp1-/- mice display an inability to rapidly repair DNA SSBs associated with Top1-DNA complexes or oxidative damage. Moreover, loss of Tdp1 resulted in age-dependent and progressive cerebellar atrophy. Tdp1-/- mice treated with topotecan, a drug that increases levels of Top1-DNA complexes, also demonstrated significant loss of intestinal and hematopoietic progenitor cells. These data indicate that TDP1 is required for neural homeostasis, and reveal a widespread requisite for TDP1 function in response to acutely elevated levels of Top1-associated DNA strand breaks. 相似文献
13.
Anticonvulsant property of Acorus calamus is known. Since combination therapy can lower the dose of individual drug and dose related toxicities, in this study, the effect of co-administration of hydroalcoholic extract of A. calamus (HAEAC) on conventional antiepileptic drugs (AEDs), sodium valproate and carbamazepine was determined using pentylenetetrazole-induced seizures model in rats. On combining the subanticonvulsant doses of HAEAC with sodium valproate and carbamazepine, greater protection as compared to either drug alone was observed. This was not related to change in levels of the AEDs. Thus, the results further substantiate anticonvulsant effect of HAEAC and suggest a potential for add on therapy with AEDs. 相似文献
14.
15.
Simsek D Brunet E Wong SY Katyal S Gao Y McKinnon PJ Lou J Zhang L Li J Rebar EJ Gregory PD Holmes MC Jasin M 《PLoS genetics》2011,7(6):e1002080
Nonhomologous end-joining (NHEJ) is the primary DNA repair pathway thought to underlie chromosomal translocations and other genomic rearrangements in somatic cells. The canonical NHEJ pathway, including DNA ligase IV (Lig4), suppresses genomic instability and chromosomal translocations, leading to the notion that a poorly defined, alternative NHEJ (alt-NHEJ) pathway generates these rearrangements. Here, we investigate the DNA ligase requirement of chromosomal translocation formation in mouse cells. Mammals have two other DNA ligases, Lig1 and Lig3, in addition to Lig4. As deletion of Lig3 results in cellular lethality due to its requirement in mitochondria, we used recently developed cell lines deficient in nuclear Lig3 but rescued for mitochondrial DNA ligase activity. Further, zinc finger endonucleases were used to generate DNA breaks at endogenous loci to induce translocations. Unlike with Lig4 deficiency, which causes an increase in translocation frequency, translocations are reduced in frequency in the absence of Lig3. Residual translocations in Lig3-deficient cells do not show a bias toward use of pre-existing microhomology at the breakpoint junctions, unlike either wild-type or Lig4-deficient cells, consistent with the notion that alt-NHEJ is impaired with Lig3 loss. By contrast, Lig1 depletion in otherwise wild-type cells does not reduce translocations or affect microhomology use. However, translocations are further reduced in Lig3-deficient cells upon Lig1 knockdown, suggesting the existence of two alt-NHEJ pathways, one that is biased toward microhomology use and requires Lig3 and a back-up pathway which does not depend on microhomology and utilizes Lig1. 相似文献
16.
Out of Africa and back again: nested cladistic analysis of human Y chromosome variation 总被引:15,自引:3,他引:15
Hammer MF; Karafet T; Rasanayagam A; Wood ET; Altheide TK; Jenkins T; Griffiths RC; Templeton AR; Zegura SL 《Molecular biology and evolution》1998,15(4):427-441
We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544
individuals from Africa, Asia, Europe, Oceania, and the New World.
Phylogenetic analyses of these nine sites resulted in a tree for 10
distinct Y haplotypes with a coalescence time of approximately 150,000
years. The 10 haplotypes were unevenly distributed among human populations:
5 were restricted to a particular continent, 2 were shared between Africa
and Europe, 1 was present only in the Old World, and 2 were found in all
geographic regions surveyed. The ancestral haplotype was limited to African
populations. Random permutation procedures revealed statistically
significant patterns of geographical structuring of this paternal genetic
variation. The results of a nested cladistic analysis indicated that these
geographical associations arose through a combination of processes,
including restricted, recurrent gene flow (isolation by distance) and range
expansions. We inferred that one of the oldest events in the nested
cladistic analysis was a range expansion out of Africa which resulted in
the complete replacement of Y chromosomes throughout the Old World, a
finding consistent with many versions of the Out of Africa Replacement
Model. A second and more recent range expansion brought Asian Y chromosomes
back to Africa without replacing the indigenous African male gene pool.
Thus, the previously observed high levels of Y chromosomal genetic
diversity in Africa may be due in part to bidirectional population
movements. Finally, a comparison of our results with those from nested
cladistic analyses of human mtDNA and beta-globin data revealed different
patterns of inferences for males and females concerning the relative roles
of population history (range expansions) and population structure
(recurrent gene flow), thereby adding a new sex-specific component to
models of human evolution.
相似文献
17.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献18.
Katyal R Rana S Singh V Vaiphei K Ojha S Singh K 《Indian journal of experimental biology》2001,39(6):546-550
To investigate the role of soyabean trypsin inhibitor (TI) during rotavirus (RV) diarrhoea, changes in enzyme activities of six relevant mucosal enzymes (lactase, sucrase, maltase, trehalase, glucoamylase and alkaline phosphatase) were assayed following inoculation of suckling mice with EB rotavirus (serotype 3) along with the TI and compared with the age-matched healthy control mice. The animals were divided into three groups i.e. group 1 (controls), group 2 (RV inoculated) and group 3 (RV + TI inoculated and sacrificed under light anaesthesia on 0, 1, 3, 5, 7 and 10 day post inoculation (dpi). Then intestines were excised and divided into two parts (jejunum and ileum). They were separately homogenized in 0.9% cold normal saline and activities of mucosal enzyme were measured. Alkaline phosphatase and disaccharidases were found to be decreased significantly in RV inoculated animals in both the anatomical portions of small intestine of mice. These enzyme levels were restored with the administration of TI i.e. in group 3 and became comparable to the controls in both intestinal portions. These studies suggest that activity of intestinal enzymes which are important in digestive absorptive functions of small intestine were restored with the addition of TI whengiven to infant mice showing its protective efficacy during rotavirus infection. 相似文献
19.
Histopathological studies of the cutaneous tissues of Wistar rats exposed to UV B radiation (294 nm) for 20 days and rats exposed to UV B radiation for 20 days, followed by topical treatment with benzoyl peroxide, a tumor promoter (20 mg/animal/0.2 ml acetone) twice a week for 1 month, and kept under observation for 12 weeks, demonstrate the development of malignancy. Pretreatment of the animals with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide (20 mg/kg bwt.), isolated from the roots of Withania somnifera, prior to exposing the animals to UV B radiation, prevents the incidence of skin carcinoma. The administration of 1-oxo-5beta, 6beta-epoxy-witha-2-enolide, to the animals after exposing them to UV B radiation/UV B radiation and benzoyl peroxide also prevents the occurrence of malignancy in the cutaneous tissue. Immunohistochemical staining of the cutaneous tissues of rats exposed to UV B radiation show the presence of p53 + foci (clusters of cells containing the mutated p53 protein), whereas an absence of p53 + foci is observed in animals pretreated with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide. These results prove that 1-oxo-5beta, 6beta-epoxy-witha-2-enolide has the potential for acting as an effective agent to prevent the incidence of skin carcinoma induced by UV B radiation. 相似文献
20.
Fate of urea-N in floodwater 总被引:2,自引:0,他引:2
One day after application, urea-N remaining in the floodwater and determined as water-soluble N (urea-N + NH4
+-N) was used to calculate the potential N loss from lowland rice soils. Actual N loss calculated from 15N balance measurements using forced air exchange (airflow rate: 20 L min-1) in greenhouse pots. Conditions for variable potential N loss were created by manipulating the method of urea application and duration of presubmergence or by selecting soils with diverse cation exchange capacities (CEC). Potential N loss tended to be lower than actual N loss; the differences were, however, nonsignificant. The method of urea application that led to the lowest potential N loss from a Guthrie silty clay loam (Typic Fragiaquult) also led to the least 15N loss and vice-versa (r=0.99**). Duration of presubmergence did not alter the relationship between potential and actual N loss although it influenced the rate of urea hydrolysis in floodwater. The primary depencence of actual N loss on water-soluble N was maintained in soils differing in CEC (r=0.83**). The association between potential and actual N loss was closer for high-CEC soils ( 20 cmol [+] kg-1 soil, r=0.91**) than for low-CEC soils (<20 cmol [+] kg-1 soil, r=0.85**). Ammonia volatilization could be more closely predicted by potential N loss than could apparent denitrification.The results of this study suggest that potential N loss calculated from one-time determination of water-soluble N in floodwater can be a good index of actual N loss from flooded, puddled rice soils. Notable exceptions are to be expected for soils in which water-soluble N gets lost from floodwater either before (soils with fast urea hydrolysis in floodwater) or after (soils with steady leaching) determination of potential N loss. 相似文献