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1.
Regulation of protein synthesis and degradation in L8 myotubes. Effects of serum, insulin and insulin-like growth factors. 总被引:5,自引:1,他引:4 下载免费PDF全文
We have examined the regulation of protein turnover in rat skeletal myotubes from the L8 cell line. We measured protein synthesis by the rates of incorporation of radiolabelled tyrosine into protein in the presence of a flooding dose of non-radioactive tyrosine. We monitored degradation of proteins labelled with radioactive tyrosine by the release of acid-soluble radioactivity into medium containing excess nonradioactive tyrosine. Extracellular tyrosine pools and intracellular tyrosyl-tRNA equilibrate rapidly during measurements of protein synthesis, and very little reutilization of the radiolabelled tyrosine occurs during degradation measurements. Measured rates of protein synthesis and degradation are constant for several hours, and changes in myotube protein content can be accurately predicted by the measured rates of protein synthesis and degradation. Most of the myotube proteins labelled with radioactive tyrosine for 2 days are degraded, with half-lives (t1/2) of approx. 50 h. A small proportion (less than 2.5%) of the radiolabelled proteins are degraded more rapidly (t1/2 less than 10 h), and, at most, a small proportion (less than 15%) are degraded more slowly (t1/2 greater than 50 h). A variety of agents commonly added to primary muscle cell cultures or to myoblast cell lines (18% Medium 199, 1% chick-embryo extract, antibiotics and antifungal agents) had no effect on rates of protein synthesis or degradation. Horse serum, fetal bovine serum and insulin stimulate protein synthesis and inhibit the degradation of long-lived proteins without affecting the degradation of short-lived proteins. Insulin-like growth factors (IGF)-1 and -2 also stimulate protein synthesis and inhibit protein degradation. The stimulation of protein synthesis and the inhibition of protein degradation are of similar magnitude (a maximum of approx. 2-fold) and display similar sensitivities to a particular anabolic agent. Insulin stimulates protein synthesis and inhibits protein degradation only at supraphysiological doses, whereas IGF-1 and -2 are effective at physiological concentrations. These and other findings suggest that IGFs may be important regulators of skeletal muscle growth during the fetal and early neonatal periods. 相似文献
2.
Cultured IMR-90 diploid human lung fibroblasts respond to withdrawal of serum or growth factors by increasing protein degradation. This increase, due to enhanced transfer of proteins into lysosomes, is specific for a class of intracellular proteins containing peptide sequences biochemically related to Lysine-Phenylalanine-Glutamate-Arginine-Glutamine (KFERQ). This peptide motif is recognized by an intracellular protein which facilitates its transfer into lysosomes in vitro and presumably, in vivo. We called this protein the peptide recognition protein of 73-kilodaltons (prp73). We have shown prp73 to be the constitutive member of the heat shock 70kD family (hsc73) by a variety of criteria. Furthermore, our reconstitution of this pathway of lysosomal degradation in vitro has provided insight in to the molecular mechanisms and requisite biochemical components. 相似文献
3.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4 下载免费PDF全文
Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
4.
We report that degradation of proteins microinjected into human fibroblasts is accompanied by release into the culture medium of peptide fragments and intact proteins as well as single amino acids. For the nine proteins and polypeptides microinjected, acid-precipitable radioactivity, i.e. peptide fragments and/or intact proteins, ranged from 10 to 67% of the total released radioactivity. Peptide fragments and/or intact protein accounted for 60% of the radioactivity released into the medium by cells microinjected with ribonuclease A. Two major radiolabeled peptide fragments were found, and one was of an appropriate size to function as an antigen in antigen-presenting cells. The peptides released from microinjected ribonuclease A were derived from lysosomal pathways of proteolysis based on several lines of evidence. Previous studies have shown that microinjected ribonuclease A is degraded to single amino acids entirely within lysosomes (McElligott, M. A., Miao, P., and Dice, J. F. (1985) J. Biol. Chem. 260, 11986-11993). We show that release of free amino acids and peptide fragments and/or intact protein was equivalently stimulated by serum deprivation and equivalently inhibited by NH4Cl. We also show that lysosomal degradation of endocytosed [3H]ribonuclease A was accompanied by the release of two peptide fragments similar in size and charge to those from microinjected [3H]ribonuclease A. These findings demonstrate that degradation within lysosomes occurs in a manner that spares specific peptides; they also suggest a previously unsuspected pathway by which cells can secrete cytosol-derived polypeptides. 相似文献
5.
6.
We compared the abilities of young and senescent fibroblasts to take up and degrade [3H]ribonuclease A (native and oxidized), [3H]ribonuclease4-13, [3H]hemoglobin, [3H]glyceraldehyde-3-phosphate dehydrogenase, [3H]beta-galactosidase, [3H]glycogen phosphorylase, and [125I]serum albumin. The endocytic uptake of these proteins ranged from fluid-phase to predominantly absorptive. Intralysosomal degradation rates of the different endocytosed proteins varied by an order of magnitude, but in no case was there a difference between cultures of young and senescent fibroblasts. 相似文献
7.
Intracellular protein degradation rates decrease with age in many tissues and organs. In cultured cells, chaperone-mediated autophagy, which is responsible for the selective degradation of cytosolic proteins in lysosomes, decreases with age. In this work we use lysosomes isolated from rat liver to analyze age-related changes in the levels and activities of the main components of chaperone-mediated autophagy. Lysosomes from "old" (22-month-old) rats show lower rates of chaperone-mediated autophagy, and both substrate binding to the lysosomal membrane and transport into lysosomes decline with age. A progressive age-related decrease in the levels of the lysosome-associated membrane protein type 2a that acts as a receptor for chaperone-mediated autophagy was responsible for decreased substrate binding in lysosomes from old rats as well as from late passage human fibroblasts. The cytosolic levels and activity of the 73-kDa heat-shock cognate protein required for substrate targeting to lysosomes were unchanged with age. The levels of lysosome-associated hsc73 were increased only in the oldest rats. This increase may be an attempt to compensate for reduced activity of the pathway with age. 相似文献
8.
Background
Most studies examining the commensal human oral microbiome are focused on disease or are limited in methodology. In order to diagnose and treat diseases at an early and reversible stage an in-depth definition of health is indispensible. The aim of this study therefore was to define the healthy oral microbiome using recent advances in sequencing technology (454 pyrosequencing). 相似文献9.
The alpha-like globin gene cluster in rabbits contains embryonic zeta-
globin genes, an adult alpha-globin gene, and theta-globin genes of
undetermined function. The basic arrangement of genes, deduced from
analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta
2-zeta 3-theta 2-3'. However, the pattern of restriction fragments
containing zeta- and theta-globin genes varies among individual rabbits.
Analysis of BamHI fragments of genomic DNA from 24 New Zealand white
rabbits revealed eight different patterns of fragments containing
zeta-globin genes. The large BamHI fragments containing genes zeta 0 and
zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the
zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary
in size. In contrast to this constancy in the size of the restriction
fragments, the copy number of the zeta 2 and zeta 3 genes does vary among
different rabbits. No length polymorphism was detected in the BamHI
fragments containing the theta-globin genes, but again the copy number
varies for restriction fragments containing the theta 2 gene. The alpha 1-
and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI
fragment. The combined data from hybridization with both zeta and theta
probes shows that the BamHI cleavage pattern does not vary within the
region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern
genomic blot-hybridization patterns for the progeny of parental rabbits
with different zeta-globin gene patterns shows that the polymorphic
patterns are inherited in a Mendelian fashion. Two different haplotypes
have been mapped based on the genomic blot-hybridization data. The
variation in the alpha-like globin gene cluster in the rabbit population
results both from differences in the copy number of the duplication block
containing the zeta-zeta-theta gene set and from the presence or absence of
polymorphic BamHI sites.
相似文献
10.
Charlie Strange Felix JF Herth Kevin L Kovitz Geoffrey McLennan Armin Ernst Jonathan Goldin Marc Noppen Gerard J Criner Frank C Sciurba 《BMC pulmonary medicine》2007,7(1):1-12