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排序方式: 共有156条查询结果,搜索用时 15 毫秒
1.
Uthayashanker R. Ezekiel Hans Peter Zassenhaus 《Molecular & general genetics : MGG》1993,240(3):414-418
We have found a cruciform cutting endonuclease in the yeast, Saccharomyces cerevisiae, which localizes to the mitochondria. This activity apparently is associated with the mitochondrial inner membrane since the activity is not released into solution by osmolysis, in contrast to the matrix enzyme, isocitrate dehydrogenase. The cruciform cutting activity appears to be encoded by CCE1. This gene has been shown to encode one of the major cruciform cutting endonucleases present in a yeast cell. In ccel strains, which lack CCE1 endonuclease activity, the mitochondrial cruciform cutting endonucleolytic activity is also absent. Since CCE1 is allelic to MGT1, a gene required for the highly biased transmission of petite mitochondrial DNA in crosses between + and hypersuppressive – cells, it seems likely that the CCE1 endonuclease functions within mitochondria. 相似文献
2.
The Triplo-Lethal Locus of Drosophila: Reexamination of Mutants and Discovery of a Second-Site Suppressor
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In the genome of Drosophila melanogaster there is a single locus, Triplo-lethal (Tpl), that causes lethality when present in either one or three copies in an otherwise diploid animal. Previous attempts to mutagenize Tpl produced alleles that were viable over a chromosome bearing a duplication of Tpl, but were not lethal in combination with a wild-type chromosome, as deficiencies for Tpl are. These mutations were interpreted as hypomorphic alleles of Tpl. In this work, we show that these alleles are not mutations at Tpl; rather, they are dominant mutations in a tightly linked, but cytologically distant, locus that we have named Suppressor-of-Tpl (Su(Tpl)). Su(Tpl) mutations suppress the lethality associated with three copies of the Triplo-lethal locus and are recessive lethal. We have mapped Su(Tpl) to the approximate map position 3-46.5, within the cytological region 76B-76D. 相似文献
3.
Analysis of lambda insertions in the fucose utilization region of Escherichia coli K-12: use of lambda fuc and lambda argA transducing bacteriophages to partially order the fucose utilization genes 总被引:8,自引:7,他引:1
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Escherichia coli K-12 strains have deletions for the normal lambda integration site were lysogenized with bacteriophage lambda at a site within the L-fucose utilization system (fuc). The frequency of lambda integration at this site is approximately 2 X 10(-8) to 5 X 10(-7). Studies of the lytic properties of these strains indicated very infrequent cell lysis with a relatively low phage burst size. Transductional ability of the phage lysates was found to be normal, comparable to that found in conventional low-frequency transducing lysates. Two major classes of transducing phage were found. One carried the markers argA and fucA (a fucose utilization gene of unknown function previously referred to as fuc-1) and the gene for D-arabinose utilization (dar+). The other carried only fucC, the gene specifying L-fuculose-1-phosphate aldolase. A minor class of phage was found that carried fucA, but not argA or dar+. Upon consideration of the transductional nature of these phage classes, we are proposing that the gene order for the L-fucose utilization system is dar, fucA, (lambda), fucC. 相似文献
4.
The structure of stryspinolactone, an unusual lactone from Strychnos spinosa, was determined from spectroscopic data. 相似文献
5.
6.
Kayode K. Ojo Ranae M. Ranade Zhongsheng Zhang David M. Dranow Janette B. Myers Ryan Choi Steve Nakazawa Hewitt Thomas E. Edwards Douglas R. Davies Donald Lorimer Stephen M. Boyle Lynn K. Barrett Frederick S. Buckner Erkang Fan Wesley C. Van Voorhis 《PloS one》2016,11(8)
We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with molecular, structural and phenotypic methods to learn if BmMetRS is a promising target for brucellosis drug development. Recombinant BmMetRS was expressed, purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP #DD-156 and screened by a thermal melt assay against a focused library of one hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood stage form of Trypanosoma brucei. Three compounds showed appreciable shift of denaturation temperature and were selected for further studies on inhibition of the recombinant enzyme activity and cell viability against wild type B. melitensis strain 16M. BmMetRS protein complexed with these three inhibitors resolved into three-dimensional crystal structures and was analyzed. All three selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS enzymatic functions in an aminoacylation assay at varying concentrations. Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS is a promising target for brucellosis drug development. However, further studies are needed to optimize lead compound potency, efficacy and safety as well as determine the pharmacokinetics, optimal dosage, and duration for effective treatment. 相似文献
7.
Gregory J. Crowther Heidi K. Hillesland Katelyn R. Keyloun Molly C. Reid Maria Jose Lafuente-Monasterio Sonja Ghidelli-Disse Stephen E. Leonard Panqing He Jackson C. Jones Mallory M. Krahn Jack S. Mo Kartheek S. Dasari Anna M. W. Fox Markus Boesche Majida El Bakkouri Kasey L. Rivas Didier Leroy Raymond Hui Gerard Drewes Dustin J. Maly Wesley C. Van Voorhis Kayode K. Ojo 《PloS one》2016,11(3)
In 2010 the identities of thousands of anti-Plasmodium compounds were released publicly to facilitate malaria drug development. Understanding these compounds’ mechanisms of action—i.e., the specific molecular targets by which they kill the parasite—would further facilitate the drug development process. Given that kinases are promising anti-malaria targets, we screened ~14,000 cell-active compounds for activity against five different protein kinases. Collections of cell-active compounds from GlaxoSmithKline (the ~13,000-compound Tres Cantos Antimalarial Set, or TCAMS), St. Jude Children’s Research Hospital (260 compounds), and the Medicines for Malaria Venture (the 400-compound Malaria Box) were screened in biochemical assays of Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4), mitogen-associated protein kinase 2 (MAPK2/MAP2), protein kinase 6 (PK6), and protein kinase 7 (PK7). Novel potent inhibitors (IC50 < 1 μM) were discovered for three of the kinases: CDPK1, CDPK4, and PK6. The PK6 inhibitors are the most potent yet discovered for this enzyme and deserve further scrutiny. Additionally, kinome-wide competition assays revealed a compound that inhibits CDPK4 with few effects on ~150 human kinases, and several related compounds that inhibit CDPK1 and CDPK4 yet have limited cytotoxicity to human (HepG2) cells. Our data suggest that inhibiting multiple Plasmodium kinase targets without harming human cells is challenging but feasible. 相似文献
8.
Vincent Kayina Samuel Kyobe Fred A. Katabazi Edgar Kigozi Moses Okee Beatrice Odongkara Harriet M. Babikako Christopher C. Whalen Moses L. Joloba Philippa M. Musoke Ezekiel Mupere 《PloS one》2015,10(4)
Background
We determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control.Methods
In a cross-sectional study, 449 children aged 3 months to 12 years with persistent cough lasting ≥14 days were enrolled and evaluated for pertussis using DNA polymerase chain reaction (PCR) and ELISA serology tests.Results
Pertussis prevalence was 67 (15% (95% Confidence Interval (CI): 12–18)) and 81 (20% (95% CI: 16–24)) by PCR and ELISA, respectively among 449 participating children. The prevalence was highest in children with >59 months of age despite high vaccination coverage of 94% in this age group. Study demographic and clinical characteristics were similar between pertussis and non-pertussis cases. Of the 449 children, 133 (30%) had a coughing household member and 316 (70%) did not. Among 133 children that had a coughing household member, sex of child, sharing bed with a coughing household member and having a coughing individual in the neighborhood were factors associated with pertussis. Children that had shared a bed with a coughing household individual had seven-fold likelihood of having pertussis compared to children that did not (odds ratio (OR) 7.16 (95% CI: 1.24–41.44)). Among the 316 children that did not have a coughing household member, age <23 months, having or contact with a coughing individual in neighborhood, a residence with one room, and having a caretaker with >40 years of age were the factors associated with pertussis. Age <23months was three times more likely to be associated with pertussis compared to age 24–59 months (OR 2.97 (95% CI: 1.07–8.28)).Conclusion
Findings suggest high prevalence of pertussis among children with persistent cough at a health facility and it was marked in children >59 months of age, suggesting the possibility of waning immunity. The factors associated with pertussis varied by presence or absence of a coughing household member. 相似文献9.
Gabriela B. Gomez Nicola Foster Daniella Brals Heleen E. Nelissen Oladimeji A. Bolarinwa Marleen E. Hendriks Alexander C. Boers Diederik van Eck Nicole Rosendaal Peju Adenusi Kayode Agbede Tanimola M. Akande Michael Boele van Hensbroek Ferdinand W. Wit Catherine A. Hankins Constance Schultsz 《PloS one》2015,10(9)
Background
While the Nigerian government has made progress towards the Millennium Development Goals, further investments are needed to achieve the targets of post-2015 Sustainable Development Goals, including Universal Health Coverage. Economic evaluations of innovative interventions can help inform investment decisions in resource-constrained settings. We aim to assess the cost and cost-effectiveness of maternal care provided within the new Kwara State Health Insurance program (KSHI) in rural Nigeria.Methods and Findings
We used a decision analytic model to simulate a cohort of pregnant women. The primary outcome is the incremental cost effectiveness ratio (ICER) of the KSHI scenario compared to the current standard of care. Intervention cost from a healthcare provider perspective included service delivery costs and above-service level costs; these were evaluated in a participating hospital and using financial records from the managing organisations, respectively. Standard of care costs from a provider perspective were derived from the literature using an ingredient approach. We generated 95% credibility intervals around the primary outcome through probabilistic sensitivity analysis (PSA) based on a Monte Carlo simulation. We conducted one-way sensitivity analyses across key model parameters and assessed the sensitivity of our results to the performance of the base case separately through a scenario analysis. Finally, we assessed the sustainability and feasibility of this program’s scale up within the State’s healthcare financing structure through a budget impact analysis. The KSHI scenario results in a health benefit to patients at a higher cost compared to the base case. The mean ICER (US$46.4/disability-adjusted life year averted) is considered very cost-effective compared to a willingness-to-pay threshold of one gross domestic product per capita (Nigeria, US$ 2012, 2,730). Our conclusion was robust to uncertainty in parameters estimates (PSA: median US$49.1, 95% credible interval 21.9–152.3), during one-way sensitivity analyses, and when cost, quality, cost and utilization parameters of the base case scenario were changed. The sustainability of this program’s scale up by the State is dependent on further investments in healthcare.Conclusions
This study provides evidence that the investment made by the KSHI program in rural Nigeria is likely to have been cost-effective; however, further healthcare investments are needed for this program to be successfully expanded within Kwara State. Policy makers should consider supporting financial initiatives to reduce maternal mortality tackling both supply and demand issues in the access to care. 相似文献10.
Contamination of soils by effluents from industries is on the increase. There is the possibility of remediating these contaminated soils through the use of certain plants. This work investigated the remediating ability of Helianthus annuus and Tithonia diversifolia on the soil polluted with effluents from a paint industry in Ibadan, Nigeria. The experiment consisted of three treatments (H. annuus, T. diversifolia, and control) each replicated three times in a factorial combination of four different fertility managements, viz mineral fertilizer (MF); Grade A organomineral fertilizer (OMF); control1, plants without fertilizer application; and control2, where no fertilizer and no crop was planted using randomized complete block design. A total of 12 plots of 2 × 4 m2 each per phytoplant were obtained. Each plot was planted with the viable seeds of the phytoplant at a spacing of 60 × 30 cm2 and at the seed rate of four seeds per hole. The seedlings were thinned to two stands per hole 2 weeks after planting (WAP) and also weeded two times (2 and 5 WAP). After in situ second successive cultivation, percentage removal of heavy metals by Helianthus annuus with MF and OMF, respectively, were Cu 32.5 and 41.6; Pb 30.3 and 42.8; and Cd 44.5 and 56.7. Tithonia diversifolia, similarly, removed, respectively, Cu 16.9 and 23.4; Pb 36.9 and 43.7; and Cd 20.1 and 35.1. Lower percentages were removed in the controls where no fertilizer was applied. In the shoot of H. annuus with OMF, significantly (p< .05) higher values of 0.27, 1.72, and 0.11 mg kg?1 of Cu, Pb, and Cd, respectively, were removed and stored at second cultivation as against 0.21, 3.39 and 0.08 mg kg?1 in the shoot of T diversifolia. Lower values of Cu, Pb, and Cd were removed with MF, and also at first cultivation with OMF and MF. This study therefore recommends the use of sunflower plants, whether hybrids or wild-types along with the application of OMF for the effective remediation of soils contaminated with heavy metals, particularly in tropical climate. 相似文献