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151.
152.
Dumoulin M Canet D Last AM Pardon E Archer DB Muyldermans S Wyns L Matagne A Robinson CV Redfield C Dobson CM 《Journal of molecular biology》2005,346(3):773-788
One of the 20 or so human amyloid diseases is associated with the deposition in vital organs of full-length mutational variants of the antibacterial protein lysozyme. Here, we report experimental data that permit a detailed comparison to be made of the behaviour of two of these amyloidogenic variants, I56T and D67H, under identical conditions. Hydrogen/deuterium exchange experiments monitored by NMR and mass spectrometry reveal that, despite their different locations and the different effects of the two mutations on the structure of the native state of lysozyme, both mutations cause a cooperative destabilisation of a remarkably similar segment of the structure, comprising in both cases the beta-domain and the adjacent C-helix. As a result, both variant proteins populate transiently a closely similar, partially unstructured intermediate in which the beta-domain and the adjacent C-helix are substantially and simultaneously unfolded, whereas the three remaining alpha-helices that form the core of the alpha-domain still have their native-like structure. We show, in addition, that the binding of a camel antibody fragment, cAb-HuL6, which was raised against wild-type lysozyme, restores to both variant proteins the stability and cooperativity characteristic of the wild-type protein; as a consequence, it inhibits the formation of amyloid fibrils by both variants. These results indicate that the reduction in global cooperativity, and the associated ability to populate transiently a specific, partly unfolded intermediate state under physiologically relevant conditions, is a common feature underlying the behaviour of these two pathogenic mutations. The formation of intermolecular interactions between lysozyme molecules that are in this partially unfolded state is therefore likely to be the fundamental trigger of the aggregation process that ultimately leads to the formation and deposition in tissue of amyloid fibrils. 相似文献
153.
154.
In this report we present the long-term follow-up findings in a young female born to consanguineous parents with the unique association of (1) a progeroid syndrome, (2) facial dysmorphism with relative microcephaly, triangular face, retrognathism and skin erythema, (3) bilateral posterior cataracts, (4) basal ganglia calcifications and (5) atrium septum defect type 2. Intelligence is borderline. Clinical evolution after normal puberty was positive with regression of the facial erythematous changes. Over the years differential diagnosis included progeria, hypohidrotic ectodermal dysplasia, Rothmund-Thompson syndrome, Cockayne syndrome, Bloom syndrome, but the clinical spectrum of abnormalities and the evolution with age were not compatible with one of these diagnoses. Parental consanguinity is in favour of autosomal recessive inheritance. 相似文献
155.
Evolution of alcohol dehydrogenase genes in peonies (Paeonia): phylogenetic relationships of putative nonhybrid species 总被引:11,自引:0,他引:11
Alcohol dehydrogenase genes were amplified by PCR, cloned, and sequenced
from 11 putative nonhybrid species of the angiosperm genus Paeonia.
Sequences of five exons and six intron regions of the Adh gene were used to
reconstruct the phylogeny of these species. Two paralogous genes, Adh1A,
and Adh2, were found; an additional gene, Adh1B, is also present in section
Moutan. Phylogenetic analyses of exon sequences of the Adh genes of Paeonia
and a variety of other angiosperms imply that duplication of Adh1 and Adh2
occurred prior to the divergence of Paeonia species and was followed by a
duplication resulting in Adh1A and Adh1B. Concerted evolution appears to be
absent between these paralogous loci. Phylogenetic analysis of only the
Paeonia Adh exon sequences, positioning the root of the tree between the
paralogous genes Adh1 and Adh2, suggests that the first evolutionary split
within the genus occurred between the shrubby section Moutan and the other
two herbaceous sections Oneapia and Paeonia. Restriction of Adh1B genes to
section Moutan may have resulted from deletion of Adh1B from the common
ancestor of sections Oneapia and Paeonia. A relative-rate test was designed
to compare rates of molecular change among lineages based on the divergence
of paralogous genes, and the results indicate a slower rate of evolution
within the shrubby section Moutan than in section Oneapia. This may be
responsible for the relatively long branch length of section Oneapia and
the short branch length between section Moutan and the other two sections
found on the Adh, ITS (nrDNA), and matK (cpDNA) phylogenies of the genus.
Adh1 and Adh2 intron sequences cannot be aligned, and we therefore carried
out separate analyses of Adh1A and Adh2 genes using exon and intron
sequences together. The Templeton test suggested that there is not
significant incongruence among Adh1A, ITS, and matK data sets, but that
these three data sets conflict significantly with Adh2 sequence data. A
combined analysis of Adh1A, ITS, and matK sequences produced a tree that is
better resolved than that of any individual gene, and congruent with
morphology and the results of artificial hybridization. It is therefore
considered to be the current best estimate of the species phylogeny.
Paraphyly of section Paeonia in the Adh2 gene tree may be caused by longer
coalescence times and random sorting of ancestral alleles.
相似文献
156.
157.
Amino acid sequence versus morphological data and the interordinal relationships of mammals 总被引:2,自引:0,他引:2
To a large extent, the mutual affinities of the mammalian orders continue
to puzzle systematists, even though comparative anatomy and amino acid
sequencing offer a massive data base from which these relationships could
potentially be adduced. In the present paper the consistency index--the
number of character states less the number of characters in a data set,
divided by the total number of changes in the character states on a
cladogram--was used to examine the relative resolving powers of recently
published morphological and molecular- sequence data. Consistency indices
were calculated for previously published alpha crystallin A chain and
myoglobin amino acid-sequence cladograms and for four original amino
acid-sequence cladograms (alpha crystallin A, myoglobin, and alpha and beta
hemoglobin); these were found to be comparable to the consistency indices
of morphologically based cladograms. Qualitative comparisons between the
morphologically based and molecularly based trees were also made; only
moderate congruence between the two was observed. Moreover, there was a
general lack of congruence between the cladograms specified by each of the
four proteins. Amino acid-sequence and morphological data agreed on the
placement of edentates as an early eutherian offshoot and on the grouping
of hyracoids, proboscideans, and sirenians. Otherwise there was only
limited congruence: morphology strongly supported the grouping of
lagomorphs and rodents and the alliance of pholidotes and edentates, but
sequence analyses did not. The placement of tubulidentates differed widely
among proteins. Morphology indicated the close association of sirenians
with proboscideans; proteins suggested a pairing of sirenians with
hyracoids. Sequence data did not identify many (morphologically
well-diagnosed) orders as monophyletic (e.g., Lagomorpha).(ABSTRACT
TRUNCATED AT 250 WORDS)
相似文献
158.
We studied urinary calcium and oxalate excretion in response to oral fructose load and to oral glucose load each on two different randomized mornings in twelve healthy subjects. Oral fructose load provoked an increase in calciuria and a decrease in oxaluria while oral glucose load induced an increase in both calciuria and oxaluria. These results suggested that in healthy subject, the decrease in oxaluria observed during fructose load reduced the product urinary [calcium] x [oxalate] which was the main factor in the genesis of urinary calcium oxalate stones while glucose load increased the risks of urolithiasis by means of the rise in both calciuria and oxaluria. 相似文献
159.
Sanchez D; Ganfornina MD; Gutierrez G; Bastiani MJ 《Molecular biology and evolution》1998,15(4):415-426
Arthropodan hemocyanins, prophenoloxidases (PPOs), and insect hexamerins
form a superfamily of hemolymph proteins that we propose to call the AHPH
superfamily. The evolutionary and functional relationships of these
proteins are illuminated by a new embryonic hemolymph protein (EHP) that is
expressed during early stages of development in the grasshopper embryo. EHP
is a 78-kDa soluble protein present initially in the yolk sac content, and
later in the embryonic hemolymph. Protein purification and peptide
sequencing were used to identify an embryonic cDNA clone coding for EHP. In
situ hybridization identifies hemocytes as EHP-expressing cells. As deduced
from the cDNA clone, EHP is a secreted protein with two potential
glycosylation sites. Sequence analysis defines EHP as a member of the AHPH
superfamily. Phylogenetic analyses with all the currently available AHPH
proteins, including EHP, were performed to ascertain the evolutionary
history of this protein superfamily. We used both the entire protein
sequence and each of the three domains present in the AHPH proteins. The
phylogenies inferred for each of the domains suggest a mosaic evolution of
these protein modules. Phylogenetic and multivariate analyses consistently
group EHP with crustacean hemocyanins and, less closely, with insect
hexamerins, relative to cheliceratan hemocyanins and PPOs. The grasshopper
protein rigorously preserves the residues involved in oxygen binding,
oligomerization, and allosteric regulation of the oxygen transport
proteins. Although insects were thought not to have hemocyanins, we propose
that EHP functions as an oxygen transport or storage protein during
embryonic development.
相似文献
160.
The use of urea as N-fertilizer for rice production has been studied for European conditions. In field and pot experiments, urea appeared to be more efficient than ammonia or nitrate. The rice yield could be maintained at maximal local production values by broadcasting 100 kg ha-1 of urea-N instead of using 200–200 kg ha-1 of ammonia or nitrate nitrogen. The best results were obtained by adding the urea about 5–8 weeks after sowing. When this was done, splitting the dose did not increase the efficiency. In laboratory experiments it was shown that urea diffuses and hydrolyses rapidly to ammonia in the anoxic layers of the flooded soils. Because this happens in the anoxic zones, the ammonia cannot be oxidised to nitrate, and is therefore less prone to denitrification, but it is adsorbed onto the soil particles. The upward diffusion of ammonia is slow, rendering it available to the rice roots for a relatively long time. The diminished use of N fertilizer is profitable for the rice farmer and helps to protect the surrounding environment. 相似文献