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41.
Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution 总被引:5,自引:0,他引:5
The fetal globin genes G gamma and A gamma from one chromosome of a
chimpanzee (Pan troglodytes) were sequenced and found to be closely similar
to the corresponding genes of man and the gorilla. These genes contain
identical promoter and termination signals and have exons 1 and 2 separated
by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the
more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G
gamma and A gamma, respectively). Each intron 2 has a stretch of simple
sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The
two chimpanzee genes encode polypeptide chains that differ only at position
136 (glycine in G gamma and alanine in A gamma) and that are identical to
the corresponding human chains, which have aspartic acid at position 73 and
lysine at 104 in contrast to glycine and arginine at these respective
positions of the gorilla A gamma chain. Phylogenetic analysis by the
parsimony method revealed four silent (synonymous) base substitutions in
evolutionary descent of the chimpanzee G gamma and A gamma codons and none
in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla)
coding sequences evolved at one-tenth the average mammalian rate for
nonsynonymous and one-fourth that for synonymous substitutions. Three
sequence regions that were affected by gene conversions between chimpanzee
G gamma and A gamma loci were identified: one extended 3' of the hot spot
with G gamma replaced by the A gamma sequence, another extended 5' of the
hot spot with A gamma replaced by G gamma, and the third conversion
extended from the 5' flanking to the 5' end of intron 2, with G gamma
replaced here by the A gamma sequence. A conversion similar to this third
one has occurred independently in the descent of the gorilla genes. The
four previously identified conversions, labeled C1-C4 (Scott et al. 1984),
were substantiated with the addition of the chimpanzee genes to our
analysis (C1 being shared by all three hominines and C2, C3, and C4 being
found only in humans). Thus, the fetal genes from all three of these
hominine species have been active in gene conversions during the descent of
each species.
相似文献
42.
1. Mouse resident peritoneal macrophages in culture modified human 125I-labelled low-density lipoprotein (LDL) to a form that other macrophages took up about 10 times as fast as unmodified LDL. The modified LDL was toxic to macrophages in the absence of serum. 2. There was a lag phase of about 4-6 h before the LDL was modified so that macrophages took it up faster. A similar time lag was observed when LDL was oxidized by 5 microM-CuSO4 in the absence of cells. 3. LDL modification was maximal when about 1.5 x 10(6) peritoneal cells were plated per 22.6 mm-diam. well. 4. Re-isolated macrophage-modified LDL was also taken up much faster by macrophages, indicating that the increased uptake was due to a change in the LDL particle itself. 5. Micromolar concentrations of iron were required for the modification of LDL by macrophages to take place. The nature of the other components in the culture medium was also important. Macrophages would modify LDL in Ham's F-10 medium but not in Dulbecco's modified Eagle's medium, even when iron was added to it. 6. The macrophage-modified LDL appeared to be taken up almost entirely via the acetyl-LDL receptor. 7. LDL modification by macrophages was inhibited partially by EDTA and desferrioxamine and completely by the general free radical scavengers butylated hydroxytoluene, vitamin E and nordihydroguaiaretic acid. It was also inhibited completely by low concentrations of foetal calf serum and by the anti-atherosclerotic drug probucol. It was not inhibited by the cyclo-oxygenase inhibitors acetylsalicylic acid and indomethacin. 8. Macrophages are a major cellular component of atherosclerotic lesions and the local oxidation of LDL by these cells may contribute to their conversion into cholesterol-laden foam cells in the arterial wall. 相似文献
43.
44.
A simple method has been set up to measure the rate of fluid-phase pinocytosis in resident mouse peritoneal macrophages in culture. The method uses 125I-labelled polyvinylpyrrolidone as a nondegradable marker of fluid-phase pinocytosis. The accumulation of 125I-labelled polyvinylpyrrolidone by the cells was directly proportional to its concentration in the culture medium up to at least 200 micrograms/ml. The estimates of the rate of fluid-phase pinocytosis were reproducible within each experiment (coefficient of variation 8.5%) but varied between individual experiments. Fluid-phase pinocytosis was undetectable at 4 degrees C and reduced greatly at 37 degrees C by metabolic inhibitors and 1 mM ZnSO4. High concentrations of human acetylated low-density lipoproteins, which are taken up rapidly by macrophages, decreased the rate of fluid-phase pinocytosis by up to about 70%. The inhibition was seen after only 2 h of incubation. Unmodified low-density lipoproteins, which are taken up only slowly by macrophages, did not usually inhibit fluid-phase pinocytosis (in fact, they sometimes increased it). Modified low-density lipoprotein uptake, leading to massive lipid accumulation in macrophages in the arterial wall, has been postulated to be involved in the pathogenesis of atherosclerosis. This study raises the possibility that the rate of fluid-phase pinocytosis in these lipid-laden arterial macrophages may be reduced. 相似文献
45.
Leake CD 《California and Western Medicine》1942,56(4):233-234
46.
47.
48.
Taylor LL Banwart SA Valdes PJ Leake JR Beerling DJ 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2012,367(1588):565-582
Global weathering of calcium and magnesium silicate rocks provides the long-term sink for atmospheric carbon dioxide (CO(2)) on a timescale of millions of years by causing precipitation of calcium carbonates on the seafloor. Catchment-scale field studies consistently indicate that vegetation increases silicate rock weathering, but incorporating the effects of trees and fungal symbionts into geochemical carbon cycle models has relied upon simple empirical scaling functions. Here, we describe the development and application of a process-based approach to deriving quantitative estimates of weathering by plant roots, associated symbiotic mycorrhizal fungi and climate. Our approach accounts for the influence of terrestrial primary productivity via nutrient uptake on soil chemistry and mineral weathering, driven by simulations using a dynamic global vegetation model coupled to an ocean-atmosphere general circulation model of the Earth's climate. The strategy is successfully validated against observations of weathering in watersheds around the world, indicating that it may have some utility when extrapolated into the past. When applied to a suite of six global simulations from 215 to 50 Ma, we find significantly larger effects over the past 220 Myr relative to the present day. Vegetation and mycorrhizal fungi enhanced climate-driven weathering by a factor of up to 2. Overall, we demonstrate a more realistic process-based treatment of plant fungal-geosphere interactions at the global scale, which constitutes a first step towards developing 'next-generation' geochemical models. 相似文献
49.
Induction of the interferon response by siRNA is cell type- and duplex length-dependent 总被引:4,自引:0,他引:4
Reynolds A Anderson EM Vermeulen A Fedorov Y Robinson K Leake D Karpilow J Marshall WS Khvorova A 《RNA (New York, N.Y.)》2006,12(6):988-993
Long (27-29-bp dsRNA) Dicer-dependent substrates have been identified as potent mediators of RNAi-induced gene knockdown in HEK293 and HeLa cells. As the lengths of these molecules are reported to be below the threshold generally regarded as necessary for induction of the mammalian interferon (IFN) response, these long siRNA are being considered as RNAi substrates in both research and therapeutic settings. In this report, we demonstrate that >23-bp dsRNA can influence cell viability and induce a potent IFN response (highlighted by a strong up-regulation of the dsRNA receptor, Toll-like receptor 3) in a cell type-specific manner. This finding suggests that the length threshold for siRNA induction of the IFN response is not fixed but instead varies significantly among different cell types. Given the diversity of cell types that comprise whole organisms, these findings suggest great care should be taken when considering length variations of dsRNA molecules for RNAi experimentation, especially in therapeutic applications. 相似文献
50.
Kettin is a high molecular mass protein of insect muscle associated with thin filaments and alpha-actinin in the Z-disc. It is thought to form a link between thin and thick filaments towards its C-terminus, contributing significantly to passive sarcomere stiffness. Here the elastic properties were characterised by mechanical stretches on an antibody-delimited region of the single molecule using two independent optical traps capable of exerting forces up to 150 pN. Step-like events were observed in the force-extension relationships consistent with the unfolding of Ig domains at moderate force and refolding of these domains at significantly higher forces than have been observed for related modular proteins. 相似文献