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41.
Phylogenetic inference under the pure drift model 总被引:1,自引:1,他引:0
When pairwise genetic distances are used for phylogenetic reconstruction,
it is usually assumed that the genetic distance between two taxa contains
information about the time after the two taxa diverged. As a result, upon
an appropriate transformation if necessary, the distance usually can be
fitted to a linear model such that it is expressed as the sum of lengths of
all branches that connect the two taxa in a given phylogeny. This kind of
distance is referred to as "additive distance." For a phylogenetic tree
exclusively driven by random genetic drift, genetic distances related to
coancestry coefficients (theta XY) between any two taxa are more suitable.
However, these distances are fundamentally different from the additive
distance in that coancestry does not contain any information about the time
after two taxa split from a common ancestral population; instead, it
reflects the time before the two taxa diverged. In other words, the
magnitude of theta XY provides information about how long the two taxa
share the same evolutionary pathways. The fundamental difference between
the two kinds of distances has led to a different algorithm of evaluating
phylogenetic trees when theta XY and related distance measures are used.
Here we present the new algorithm using the ordinary- least-squares
approach but fitting to a different linear model. This treatment allows
genetic variation within a taxon to be included in the model. Monte Carlo
simulation for a rooted phylogeny of four taxa has verified the efficacy
and consistency of the new method. Application of the method to human
population was demonstrated.
相似文献
42.
Nisin biosynthesis genes are encoded by a novel conjugative transposon 总被引:17,自引:0,他引:17
Nikki Horn Simon Swindell Helen Dodd Michael Gasson 《Molecular & general genetics : MGG》1991,228(1-2):129-135
Summary Genes for biosynthesis of the lactococcal peptide antibiotic nisin were shown to be encoded by a novel chromosomally located transposon Tn5301. The element is 70 kb in size and lacks inverted repeats at its termini. Although a copy of the insertion sequence IS904 is located near to one end, this did not appear to be involved in the transposition process. The integrated element is flanked by the directly repeated sequence 5-TTTTTG-3. Analysis of ten independent transconjugants revealed that Tn5301 integration is site-specific; two chromosomal targets were identified and shown to have some sequence homology. The element shares features with the Tn916 family of conjugative transposons and with Tn554 but is also exhibits some unique properties. Tn5301 is thus considered to be the prototype of a novel class of conjugative transposon. 相似文献
43.
Evaluation and clinical relevance of patient immune responses to intravenous therapy with murine monoclonal antibodies conjugated to adriamycin 总被引:1,自引:0,他引:1
B Avner L Swindell E Sharp S K Liao J R Ogden B P Avner R K Oldham 《Molecular biotherapy》1991,3(1):14-21
A retrospective study was performed in order to examine the clinical relevance of human anti-murine antibodies (HAMA) to concurrent clinical events in 21 patients receiving intravenous therapy with cocktails of murine monoclonal antibodies conjugated to Adriamycin. In vivo tumor localization of the murine antibodies was also evaluated. Serum levels of HAMA, human-murine immune complexes (HMIC), and murine antibodies were measured using an automated fluorescence immunoassay. Immunohistochemical staining was performed on frozen sections of tumor biopsies from eight of the patients to examine the in vivo binding of the murine antibodies. The patients were divided into low, intermediate, and high antibody dose groups. The incidence of allergic symptoms (80%) and HAMA correlation (75%) were highest in the low dose group. Specific IgM HAMA was the most highly correlated with allergic reactions, being present in 61.5% of the allergic patients. Thirteen of the 21 patients studied (61.9%) developed allergic symptoms after one or more doses of the murine monoclonal antibody conjugates. The percentages of total antibody doses in the patients' sera at varying intervals post-infusion varied widely from patient to patient for any given time point and dose, suggesting complex factors in the distribution and clearance of the murine antibodies. All eight of the patients biopsied during or post-therapy exhibited tumor localization of the murine monoclonal antibodies. Six of the eight had concurrent HAMA in their sera. Thus, the presence of HAMA did not prevent in vivo localization of the murine antibodies in the target tumors.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Pearson KJ Baur JA Lewis KN Peshkin L Price NL Labinskyy N Swindell WR Kamara D Minor RK Perez E Jamieson HA Zhang Y Dunn SR Sharma K Pleshko N Woollett LA Csiszar A Ikeno Y Le Couteur D Elliott PJ Becker KG Navas P Ingram DK Wolf NS Ungvari Z Sinclair DA de Cabo R 《Cell metabolism》2008,8(2):157-168
A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging, including reduced albuminuria, decreased inflammation, and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife. 相似文献
47.
Gene flow among historically isolated populations is expected to increase genetic diversity and consequently the ability of
populations to adapt to environmental changes. Few experimental studies, however, have examined the relationship between gene
flow and the adaptive potential of populations. The increase in adaptive potential that occurs as a result of gene flow is
expected to depend on the genetic variance among populations that undergo genetic exchange. In the present study, we compared
observed and expected changes in adaptive potential (as measured by the selection response of sternopleural bristle number)
that occur as a result of gene flow among experimental populations of Drosophila melanogaster. We examined the effect of limited immigration (m = 0.05 over 3 generations) among a set of experimentally isolated lineages, in addition to the effect of complete hybridization
among lineages. As expected, we found that limited immigration and hybridization both yielded increases in adaptive potential.
However, whereas the effect of limited immigration agreed well with theoretical expectations, the increase in adaptive potential
following complete hybridization of lineages was significantly less than expected. We discuss these findings in relation to
endangered species conservation efforts, particularly with respect to the goal of maximizing the retention of adaptive potential
within managed populations. 相似文献
48.
Agata I. Rembielak Pooja Jain Andrew S. Jackson Melanie M. Green Gillian R. Santorelli Gillian A. Whitfield Adrian Crellin Angel Garcia-Alonso Ganesh Radhakrishna James Cullen M. Ben Taylor Ric Swindell Catharine M. West Juan Valle Azeem Saleem Patricia M. Price 《Translational oncology》2014,7(1):55-64
BACKGROUND: Preclinical data have indicated the anti-epidermal growth factor receptor (EGFR) agent cetuximab (Erbitux) as a radiosensitizer in pancreatic cancer, but this has not been specifically addressed in a clinical study. We report the results of an original study initiated in 2007, where cetuximab was tested with radiotherapy (RT) alone in locally advanced pancreatic cancer in a phase II trial (PACER). METHODS: Patients (n = 21) received cetuximab loading dose (400 mg/m2) and weekly dose (250 mg/m2) during RT (50.4 Gy in 28 fractions). Toxicity and disease response end point data were prospectively assessed. A feasibility study of on-trial patient blood and skin sampling was incorporated. RESULTS: Treatment was well tolerated, toxicity was low; most patients (71%) experienced acute toxicities of grade 2 or less. Six months posttreatment, stable local disease was achieved in 90% of evaluable patients, but only 33% were free from metastatic progression. Median overall survival was 7.5 months, actuarial survival was 33% at 1 year and 11% at 3 years, reflecting swift metastatic progression in some patients but good long-term control of localized disease in others. High-grade acneiform rash (P = .0027), posttreatment stable disease (P = .0059), pretreatment cancer antigen 19.9 (CA19.9) level (P = .0042) associated with extended survival. Patient skin and blood samples yielded sufficient RNA and good quality protein, respectively. CONCLUSIONS: The results indicate that cetuximab inhibits EGFR-mediated radioresistance to achieve excellent local control with minimal toxicity but does not sufficiently control metastatic progression in all patients. Translational studies of patient tissue samples may yield molecular information that may enable individual treatment response prediction. 相似文献
49.
Crispld2 is required for neural crest cell migration and cell viability during zebrafish craniofacial development
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Eric C. Swindell Qiuping Yuan Lorena E. Maili Bhavna Tandon Daniel S. Wagner Jacqueline T. Hecht 《Genesis (New York, N.Y. : 2000)》2015,53(10):660-667
The CAP superfamily member, CRISPLD2, has previously been shown to be associated with nonsyndromic cleft lip and palate (NSCLP) in human populations and to be essential for normal craniofacial development in the zebrafish. Additionally, in rodent models, CRISPLD2 has been shown to play a role in normal lung and kidney development. However, the specific role of CRISPLD2 during these developmental processes has yet to be determined. In this study, it was demonstrated that Crispld2 protein localizes to the orofacial region of the zebrafish embryo and knockdown of crispld2 resulted in abnormal migration of neural crest cells (NCCs) during both early and late time points. An increase in cell death after crispld2 knockdown as well as an increase in apoptotic marker genes was also shown. This data suggests that Crispld2 modulates the migration, differentiation, and/or survival of NCCs during early craniofacial development. These results indicate an important role for Crispld2 in NCC migration during craniofacial development and suggests involvement of Crispld2 in cell viability during formation of the orofacies. genesis 53:660–667, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
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