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141.
Willem J. De Lange Adrian C. Grimes Laura F. Hegge Alexander M. Spring Taylor M. Brost J. Carter Ralphe 《The Journal of general physiology》2013,142(3):241-255
Mutations in cardiac myosin binding protein C (cMyBP-C) are prevalent causes of hypertrophic cardiomyopathy (HCM). Although HCM-causing truncation mutations in cMyBP-C are well studied, the growing number of disease-related cMyBP-C missense mutations remain poorly understood. Our objective was to define the primary contractile effect and molecular disease mechanisms of the prevalent cMyBP-C E258K HCM-causing mutation in nonremodeled murine engineered cardiac tissue (mECT). Wild-type and human E258K cMyBP-C were expressed in mECT lacking endogenous mouse cMyBP-C through adenoviral-mediated gene transfer. Expression of E258K cMyBP-C did not affect cardiac cell survival and was appropriately incorporated into the cardiac sarcomere. Functionally, expression of E258K cMyBP-C caused accelerated contractile kinetics and severely compromised twitch force amplitude in mECT. Yeast two-hybrid analysis revealed that E258K cMyBP-C abolished interaction between the N terminal of cMyBP-C and myosin heavy chain sub-fragment 2 (S2). Furthermore, this mutation increased the affinity between the N terminal of cMyBP-C and actin. Assessment of phosphorylation of three serine residues in cMyBP-C showed that aberrant phosphorylation of cMyBP-C is unlikely to be responsible for altering these interactions. We show that the E258K mutation in cMyBP-C abolishes interaction between N-terminal cMyBP-C and myosin S2 by directly disrupting the cMyBP-C–S2 interface, independent of cMyBP-C phosphorylation. Similar to cMyBP-C ablation or phosphorylation, abolition of this inhibitory interaction accelerates contractile kinetics. Additionally, the E258K mutation impaired force production of mECT, which suggests that in addition to the loss of physiological function, this mutation disrupts contractility possibly by tethering the thick and thin filament or acting as an internal load. 相似文献
142.
Patrick Knott Eden Pappo Michelle Cameron JC deMauroy Charles Rivard Tomasz Kotwicki Fabio Zaina James Wynne Luke Stikeleather Josette Bettany-Saltikov Theodoros B Grivas Jacek Durmala Toru Maruyama Stefano Negrini Joseph P O’Brien Manuel Rigo 《Scoliosis》2014,9(1):1-9
This 2012 Consensus paper reviews the literature on side effects of x-ray exposure in the pediatric population as it relates to scoliosis evaluation and treatment. Alternative methods of spinal assessment and imaging are reviewed, and strategies for reducing the number of radiographs are developed. Using the Delphi technique, SOSORT members developed consensus statements that describe how often radiographs should be taken in each of the pediatric and adolescent sub-populations. 相似文献
143.
The concentrations of Fe, Mn, Ni, Pb and V in water, sediment and the gill, liver and muscle tissues of Synodontis resupinatus, Heterotis niloticus and Clarias gariepinus, all commercially important fish species of the lower Niger River, were investigated in 2015. Water, sediment and fish samples were collected for six months and heavy metals were determined using an Atomic Absorption Spectrometer. Fe ranked highest in water and sediment, with concentrations of 2.74 mg l?1 and 61.60 mg kg?1, respectively. Metals followed the magnitude of Fe > Mn > Ni > V > Pb in the water and Fe > Mn > V > Ni > Pb in the sediments. Metal concentrations were higher in the tissues of S. resupinatus compared with H. niloticus and C. gariepinus. Fe was also highest in the gills, liver and muscle of the three fish species. Its highest concentration of 132.97 mg kg?1 dry weight was recorded in the gills of S. resupinatus. Bioconcentration factors of metals ranged from 8.79 for Mn in H. niloticus muscle to 67.99 for Ni in S. resupinatus gills. The fish species studied pose no health risk for all metals studied, because the target hazard quotient was less than 1 and the estimated daily intakes of the metals were below the reference doses. 相似文献
144.
A nuclear gene for higher level phylogenetics: phosphoenolpyruvate carboxykinase tracks mesozoic-age divergences within Lepidoptera (Insecta) 总被引:3,自引:0,他引:3
The sequence of phosphoenolpyruvate carboxykinase (PEPCK) has been
previously identified as a promising candidate for reconstructing
Mesozoic-age divergences (Friedlander, Regier, and Mitter 1992, 1994). To
test this hypothesis more rigorously, 597 nucleotides of aligned PEPCK
coding sequence (approximately 30% of the coding region) were generated
from 18 species representing Mesozoic-age lineages of moths (Insecta:
Lepidoptera) and outgroup taxa. Relationships among basal Lepidoptera are
well established by morphological analysis, providing a strong test for the
utility of a gene which has not previously been used in systematics.
Parsimony and other phylogenetic analyses were conducted on nucleotides by
codon positions (nt1, nt2, nt3) separately and in combination, and on amino
acids, for comparison to the test phylogeny. The highest concordance was
achieved with nt1 + nt2, for which one of two most-parsimonious trees was
identical to the test phylogeny, and with all nucleotides when nt3 was
down-weighted sevenfold or higher, for which a single most-parsimonious
tree identical to the test phylogeny resulted. Substitutions in nt3
approached saturation in many, but not all, pairwise comparisons and their
exclusion or severe downweighting greatly increased the degree of
concordance with the test phylogeny. Neighbor-joining analysis confirms
this finding. The utility of PEPCK for phylogenetics is demonstrated over a
time span for which few other suitable genes are currently available.
相似文献
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148.
Esther Munalula‐Nkandu Paul Ndebele Seter Siziya JC Munthali 《Developing world bioethics》2015,15(3):248-256
We conducted a study to review the consenting process in a vaginal Microbicide feasibility study conducted in Mazabuka, Zambia. Participants were drawn from those participating in the microbicide study. A questionnaire and focus group discussion were used to collect information on participants understanding of study aims, risks and benefits. Altogether, 200 participants took part in this study. The results of the study showed that while all participants signed or endorsed their thumbprints to the consent forms, full informed consent was not attained from most of the participants since 77% (n = 154) of the participants had numerous questions about the study and 34% (n = 68) did not know who to get in touch with concerning the study. Study objectives were not fully understood by over 61% of the participants. Sixty four percent of the participants were not sure of the risks of taking part in the microbicide study. A significant number thought the study was all about determining their HIV status. Some participants were concerned that their partners were not on the trial as they were convinced that being on the study meant that that they had a lifetime protection from HIV infection. The process of obtaining consent was inadequate as various phases of the study were not fully understood. We recommend the need for researchers to reinforce the consenting process in all studies and more so when studies are conducted in low literacy populations. 相似文献
149.
Avise JC; Shapira JF; Daniel SW; Aquadro CF; Lansman RA 《Molecular biology and evolution》1983,1(1):38-56
We address the problem of the possible significance of biological
speciation to the magnitude and pattern of divergence of asexually
transmitted characters in bisexual species. The empirical data for this
report consist of restriction endonuclease site variability in maternally
transmitted mitochondrial DNA (mtDNA) isolated from 82 samples of
Peromyscus polionotus and P. leucopus collected from major portions of the
respective species' ranges. Data are analyzed together with previously
published information on P. maniculatus, a sibling species to polionotus.
Maps of restriction sites indicate that all of the variation observed can
be reasonably attributed to base substitutions leading to loss or gain of
particular recognition sites. Magnitude of mtDNA sequence divergence within
polionotus (maximum approximately equal to 2%) is roughly comparable to
that observed within any of five previously identified mtDNA assemblages in
maniculatus. Sequence divergence within leucopus (maximum approximately
equal to 4%) is somewhat greater than that within polionotus. Consideration
of probable evolutionary links among mtDNA restriction site maps allowed
estimation of matriarchal phylogenies within polionotus and leucopus.
Clustering algorithms and qualitative Wagner procedures were used to
generate phenograms and parsimony networks, respectively, for the
between-species comparisons. Three simple graphical models are presented to
illustrate some conceivable relationships of mtDNA differentiation to
speciation. In theoretical case I, each of two reproductively defined
species (A and B) is monophyletic in matriarchal genealogy; the common
female ancestor of either species can either predate or postdate the
speciation. In case II, neither species is monophyletic in matriarchal
genotype. In case III, species B is monophyletic but forms a subclade
within A which is thus paraphyletic with respect to B. The empirical
results for mtDNA in maniculatus and polionotus appear to conform closely
to case III. These theoretical and empirical considerations raise a number
of questions about the general relationship of the speciation process to
the evolution of uniparentally transmitted traits. Some of these
considerations are presented, and it is suggested that the distribution
patterns of mtDNA sequence variation within and among extant species should
be of considerable relevance to the particular demographies of speciation.
相似文献
150.
Accessing genetic diversity for crop improvement 总被引:1,自引:0,他引:1