全文获取类型
收费全文 | 207篇 |
免费 | 25篇 |
出版年
2021年 | 4篇 |
2018年 | 2篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 7篇 |
2013年 | 8篇 |
2012年 | 15篇 |
2011年 | 13篇 |
2010年 | 7篇 |
2009年 | 6篇 |
2008年 | 5篇 |
2007年 | 7篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 6篇 |
1999年 | 12篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 6篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1975年 | 4篇 |
1974年 | 1篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1966年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有232条查询结果,搜索用时 15 毫秒
1.
J R Foulkes 《BMJ (Clinical research ed.)》1981,283(6300):1172-1174
2.
Embryonal carcinoma-derived growth factor activates protein kinase C in vivo and in vitro. 总被引:4,自引:0,他引:4 下载免费PDF全文
We have recently reported that a polypeptide mitogen, the embryonal carcinoma-derived growth factor (ECDGF), induces phosphorylation of the epidermal growth factor (EGF) receptor in intact C3H 10T 1/2 mouse fibroblasts with concomittant loss of high affinity EGF binding sites. This phenomenon appears to be mediated through an activation of protein kinase C. Several groups have described an acidic 80,000 dalton protein substrate of protein kinase C. In this paper, we demonstrate that the addition of ECDGF or the phorbol ester TPA to intact C3H 10T 1/2 cells results in the enhanced phosphorylation of this 80 kd protein in vivo. Furthermore, this response is demonstrable in vitro. Thus the addition of ECDGF, the phorbol ester TPA, protein kinase C or phosphoinositidase C to crude membranes prepared from C3H 10T 1/2 cells resulted in the enhanced phosphorylation of this protein. Data obtained by phosphopeptide mapping of the 80 kd protein show that the ECDGF-induced activation of protein kinase C in our membrane preparations is comparable with that obtained in vivo. The availability of an in vitro system in which this response is preserved should now allow a detailed biochemical analysis of the steps between binding of a mitogen to its receptor and the activation of protein kinase C. 相似文献
3.
E. C. Foulkes 《Biological trace element research》1989,21(1):195-200
Review of the available evidence on the mechanism of cellular Cd uptake in the rat jejunum supports the concept that this
process consists of nonspecific binding to anionic sites on the membrane, followed by a temperature-dependent and rate-limiting
internalization step. Because temperature-sensitive transmembrane movement of Cd can be demonstrated also in isolated brush-border
vesicles and in erythrocyte ghosts, it is not likely to result from pinocytosis but may be related directly to membrane fluidity.
There is no need to assume the existence of saturable Cd carriers, or competition of Cd with essential polyvalent cations
for their specific transport systems. Uptake of Cd by tubular epithelium in the kidney of the intact rabbit appears to resemble
that described for the jejunum, with the internalization step limiting the rate of uptake. 相似文献
4.
5.
W J Gullick J Downward J G Foulkes M D Waterfield 《European journal of biochemistry》1986,158(2):245-253
A region of the primary amino acid sequence of the epidermal growth factor receptor (EGF) protein-tyrosine kinase, which is involved in ATP binding, was identified using chemical modification and immunological techniques. EGF receptor was 14C-labelled with the ATP analogue 5'-p-fluorosulphonylbenzoyladenosine and from a tryptic digest a single radiolabelled peptide was isolated. The amino acid sequence was determined to be residues 716-724 and hence lysine residue 721 is located within the ATP-binding site. Antisera were elicited in rabbits to a synthetic peptide identical to residues 716-727 of the EGF receptor and the homologous sequence in v-erb B transforming protein from avian erythroblastosis virus. The affinity-purified antibodies precipitated human ECF receptor from A431 cells and placenta, and the v-erb B protein from erythroblasts. The antibodies inhibited EGF-stimulated receptor protein-tyrosine kinase autophosphorylation and phosphorylation of an exogenous peptide substrate containing tyrosine. The antibodies did not immunoprecipitate the transforming proteins pp60v-src or P120gag-abl or cAMP-dependent protein kinase, proteins which have homologous but not identical sequences surrounding the lysine residue within the ATP-binding site, nor did they react with the platelet-derived growth factor receptor. The antibodies had no effect on the kinase activity of purified v-abl protein in solution. The antibodies may therefore be a specific inhibitor of the tyrosine kinase of the EGF receptor. 相似文献
6.
A kinetic analysis of the effects of inhibitor-1 and inhibitor-2 on the activity of protein phosphatase-1 总被引:1,自引:0,他引:1
The steady-state interaction between protein phosphatase-1 and its two inhibitor proteins was studied in vitro at low enzyme concentrations where the assumptions of the Michaelis-Menten equation appeared to be valid. Under these conditions, and in the absence of divalent cations, inhibitor-1 behaved as a mixed inhibitor using phosphorylase alpha as a substrate, whereas inhibitor-2 was a competitive inhibitor. The results demonstrate that inhibitor-1 and inhibitor-2 do not interact with protein phosphatase-1 in an identical manner. Inhibitor-1 was only a substrate for protein phosphatase-1 in the presence of Mn2+, and its dephosphorylation was inhibited competitively by inhibitor-2 (Kis = 8 nM). Inhibitor-1 did not inhibit its own dephosphorylation in the presence of Mn2+. Its Km as a substrate (190 nM) was very much higher than its Ki as an inhibitor (1.5-7.5 nM). The results are consistent with a model in which a single binding site for inhibitor-1 is present on protein phosphatase-1, distinct from the binding site for phosphorylase alpha. It is envisaged that the binding of inhibitor-1 to this site not only inhibits the dephosphorylation of other substrates but permits access of its phosphothreonine to the same catalytic group(s) responsible for the dephosphorylation of other substrates. G-substrate, a protein phosphorylated exclusively on threonine residues, did not inhibit the dephosphorylation of phosphorylase alpha and its dephosphorylation was potently inhibited by inhibitor-1 or inhibitor-2. The role of the phosphothreonine residue in inhibitor-1 is discussed in the light of these results. 相似文献
7.
Sequences of the A-MuLV protein needed for fibroblast and lymphoid cell transformation 总被引:57,自引:0,他引:57
The role of various segments (gag or v-abl) of the Abelson murine leukemia virus (A-MuLV) genome in both lymphoid cell and fibroblast transformation was examined by deletion of areas from cloned, plasmid DNA representations of the genome. The deleted plasmids were tested by transfection into fibroblasts and by infection of bone marrow cells using virus stocks derived from the fibroblast transfectants. Deletion of gag coding sequence from the A-MuLV protein did not affect fibroblast transforming activity but abolished lymphoid transforming activity. The gag- A-MuLV genomes were very unstable in transformed fibroblasts leading to large secondary deletions in v-abl sequences. The gag- A-MuLV proteins also had lower autophosphorylation than their gag+ counterparts although cells transformed by gag- virus had a normal elevation of protein-linked phosphotyrosine. Systematic deletion of v-abl sequences showed that only 45,000 to the 130,000 molecular weight of v-abl sequence in the A-MuLV protein is needed for fibroblast transformation and, at most, slightly more is needed for lymphoid cell transformation. 相似文献
8.
9.
We have broadly defined the DNA regions regulating esterase6 activity in
several life stages and tissue types of D. melanogaster using P-
element-mediated transformation of constructs that contain the esterase6
coding region and deletions or substitutions in 5' or 3' flanking DNA.
Hemolymph is a conserved ancestral site of EST6 activity in Drosophila and
the primary sequences regulating its activity lie between -171 and -25 bp
relative to the translation initiation site: deletion of these sequences
decrease activity approximately 20-fold. Hemolymph activity is also
modulated by four other DNA regions, three of which lie 5' and one of which
lies 3' of the coding region. Of these, two have positive and two have
negative effects, each of approximately twofold. Esterase6 activity is
present also in two male reproductive tract tissues; the ejaculatory bulb,
which is another ancestral activity site, and the ejaculatory duct, which
is a recently acquired site within the melanogaster species subgroup.
Activities in these tissues are at least in part independently regulated:
activity in the ejaculatory bulb is conferred by sequences between -273 and
-172 bp (threefold decrease when deleted), while activity in the
ejaculatory duct is conferred by more distal sequences between -844 and
-614 bp (fourfold decrease when deleted). The reproductive tract activity
is further modulated by two additional DNA regions, one in 5' DNA (-613 to
-284 bp; threefold decrease when deleted) and the other in 3' DNA (+1860 to
+2731 bp; threefold decrease when deleted) that probably overlaps the
adjacent esteraseP gene. Collating these data with previous studies
suggests that expression of EST6 in the ancestral sites is mainly regulated
by conserved proximal sequences while more variable distal sequences
regulate expression in the acquired ejaculatory duct site.
相似文献
10.
Nucleotide variation at the hypervariable esterase 6 isozyme locus of Drosophila simulans 总被引:2,自引:0,他引:2
Esterase 6 (Est-6/EST6) is polymorphic in both Drosophila melanogaster and
D. simulans for two common allozyme forms, as well as for several other
less common variants. Parallel latitudinal clines in the frequencies of the
common EST6-F and EST6-S allozymes in these species have previously been
interpreted in terms of a shared amino acid polymorphism that distinguishes
the two variants and is subject to selection. Here we compare the sequences
of four D. simulans Est-6 isolates and show that overall estimates of
nucleotide heterozygosity in both coding and 5' flanking regions are more
than threefold higher than those obtained previously for this gene in D.
melanogaster. Nevertheless, the ratio of replacement to exon silent-site
polymorphism in D. simulans is less than the ratio of replacement to silent
divergence between D. simulans and D. melanogaster, which could be the
result of increased efficiency of selection against replacement
polymorphisms in D. simulans or to divergent selection between the two
species. We also find that the amino acid polymorphisms separating EST6- F
and EST6-S in D. simulans are not the same as those that separate these
allozymes in D. melanogaster, implying that the shared clines do not
reflect shared molecular targets for selection. All comparisons within and
between the two species reveal a remarkable paucity of variation in a
stretch of nearly 400 bp immediately 5' of the gene, indicative of strong
selective constraint to retain essential aspects of Est-6 promoter
function.
相似文献