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61.
Two different regions of P-glycoprotein [corrected] are photoaffinity-labeled by azidopine 总被引:4,自引:0,他引:4
E P Bruggemann U A Germann M M Gottesman I Pastan 《The Journal of biological chemistry》1989,264(26):15483-15488
Cells that express P-glycoprotein are resistant to many unrelated anticancer drugs. All evidence suggests that P-glycoprotein is a plasma membrane protein that confers multidrug resistance by actively transporting these cytotoxic drugs out of cells. The objective of our work is to locate drug binding sites on P-glycoprotein. Azidopine is a photoaffinity drug analog that specifically labels P-glycoprotein. To determine the region of P-glycoprotein that binds azidopine, we labeled P-glycoprotein with azidopine and digested the labeled protein into fragments. We then identified the labeled fragments with specific antibodies. We have determined that azidopine labels two different regions of P-glycoprotein: one region is in the amino half of P-glycoprotein, and the other is in the carboxyl half of the protein. Our results suggest that P-glycoprotein contains either two binding sites for azidopine or a single site formed by the two homologous halves of the protein. 相似文献
62.
Isolation and structural organization of the Neurospora crassa copper metallothionein gene. 总被引:9,自引:1,他引:8
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The Neurospora crassa copper metallothionein gene was cloned and its complete nucleotide sequence is reported. Enriched metallothionein mRNA was used as a template for cDNA synthesis, primed by a metallothionein-specific, synthetic undecanucleotide. The sequence of the cDNA obtained allowed the synthesis of a unique 21-mer which was used to screen a genomic DNA library of N. crassa. In agreement with the published amino acid sequence, the gene codes for a polypeptide 26 amino acid residues in length. The coding region is interrupted by a small intron (94 nucleotides). The gene structure is compared with those of mammalian metallothioneins. In both cases, the coding regions are split by introns, the intron-exon boundaries, however, are in different positions. The neurospora copper metallothionein gene is, to our knowledge, the smallest gene interrupted by an intron isolated so far. 相似文献
63.
Tempo and mode of concerted evolution in the L1 repeat family of mice 总被引:10,自引:0,他引:10
Martin SL; Voliva CF; Hardies SC; Edgell MH; Hutchison CA d 《Molecular biology and evolution》1985,2(2):127-140
A 300-bp DNA sequence has been determined for 30 (10 from each of three
species of mice) random isolates of a subset of the long interspersed
repeat family L1. From these data we conclude that members of the L1 family
are evolving in concert at the DNA sequence level in Mus domesticus, Mus
caroli, and Mus platythrix. The mechanism responsible for this phenomenon
may be either duplicative transposition, gene conversion, or a combination
of the two. The amount of intraspecies divergence averages 4.4%, although
between species base substitutions accumulate at the rate of approximately
0.85%/Myr to a maximum divergence of 9.1% between M. platythrix and both M.
domesticus and M. caroli. Parsimony analysis reveals that the M. platythrix
L1 family has evolved into a distinct clade in the 10-12 Myr since M.
platythrix last shared a common ancestor with M. domesticus and M. caroli.
The parsimony tree also provides a means to derive the average half-life of
L1 sequences in the genome. The rates of gain and loss of individual copies
of L1 were estimated to be approximately equal, such that approximately
one-half of them turn over every 3.3 Myr.
相似文献
64.
The HP1 family proteins are involved in several aspects of chromatin function and regulation in Drosophila, mammals and the
fission yeast. Here we investigate the localization of LHP1, the unique Arabidopsis thaliana HP1 homolog known at present time, to approach its function. A functional LHP1–GFP fusion protein, able to restore the wild-type
phenotype in the lhp1 mutant, was used to analyze the subnuclear distribution of LHP1 in both A. thaliana and Nicotiana tabacum. In A. thaliana interphase nuclei, LHP1 was predominantly located outside the heterochromatic chromocenters. No major aberrations were observed
in heterochromatin content or chromocenter organization in lhp1 plants. These data indicate that LHP1 is mainly involved in euchromatin organization in A. thaliana. In tobacco BY-2 cells, the LHP1 distribution, although in foci, slightly differed suggesting that LHP1 localization is determined
by the underlying genome organization of plant species. Truncated LHP1 proteins expressed in vivo allowed us to determine
the function of the different segments in the localization. The in foci distribution is dependent on the presence of the two
chromo domains, whereas the hinge region has some nucleolus-targeting properties. Furthermore, like the animal HP1β and HP1γ
subtypes, LHP1 dissociates from chromosomes during mitosis. In transgenic plants expressing the LHP1–GFP fusion protein, two
major localization patterns were observed according to cell types suggesting that localization evolves with age or differentiation
states. Our results show conversed characteristics of the A. thaliana HP1 homolog with the mammal HP1γ isoform, besides specific plant properties. 相似文献
65.
B. Thöny F. Neuheiser L. Kierat M. O. Rolland P. Guibaud T. Schlüter R. Germann R. A. Heidenreich M. Duran J. B. C. de Klerk J. E. Ayling N. Blau 《Human genetics》1998,103(2):162-167
Four patients with primapterinuria, postulated to be due to pterin-4α-carbinolamine dehydratase (PCD) deficiency, were diagnosed
by biochemical and DNA analysis. All four patients presented in the neonatal period with hyperphenylalaninemia, and elevated
neopterin and decreased biopterin levels in the urine. These symptoms are common to 6-pyruvoyltetrahydropterin synthase deficiency
and thus there is a danger of misdiagnosis. In addition, all four patients had elevated urinary excretion of primapterin (7-biopterin),
the only persistent biochemical abnormality. Analysis of fibroblast DNA from the patients identified the following mutations
in the PCBD gene: one patient homozygous for the missense mutation E96K and one homozygous for the nonsense mutation Q97X, both in exon
4; one compound heterozygote with the mutations E96K and Q97X; and one patient with two different homozygous mutations: E26X
in exon 2 and R87Q in exon 4. In two families, the parents were investigated and found to be obligate heterozygotes for particular
mutations. One sibling was found to be unaffected. These results further substantiate the idea that primapterinuria is associated
with mutations in the PCBD gene.
Received: 4 March 1998 / Accepted: 17 April 1998 相似文献
66.
67.
Marina Evich Ekaterina Stroeva Yujun George Zheng Markus W. Germann 《Protein science : a publication of the Protein Society》2016,25(2):479-486
Arginine methylation is important in biological systems. Recent studies link the deregulation of protein arginine methyltransferases with certain cancers. To assess the impact of methylation on interaction with other biomolecules, the pKa values of methylated arginine variants were determined using NMR data. The pKa values of monomethylated, symmetrically dimethylated, and asymmetrically dimethylated arginine are similar to the unmodified arginine (14.2 ± 0.4). Although the pKa value has not been significantly affected by methylation, consequences of methylation include changes in charge distribution and steric effects, suggesting alternative mechanisms for recognition. 相似文献
68.
Differentiation of two distinct K conductances in the basolateral membrane of turtle colon 总被引:2,自引:0,他引:2
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The K conductance of the basolateral membrane of turtle colon was measured in amphotericin-treated cell layers under a variety of ionic conditions. Changing the composition of the bathing solutions changed not only the magnitude but also the physical properties of the basolateral K conductance. The results are consistent with the notion that altered ionic environments can lead to changes in the relative abundance of two different populations of K channels in the basolateral membrane, which can be differentiated on the basis of pharmacological specificity, ion selectivity, and tracer kinetics. In the following article (Germann, W. J., S. A. Ernst, and D. C. Dawson, 1986, Journal of General Physiology, 88:253-274), we present evidence consistent with the hypothesis that one of these conductances was due to the same channels that give rise to the normal resting basolateral K conductance of the transporting cells, while the other was associated with experimental maneuvers that led to extreme swelling of the epithelial cells. 相似文献
69.
A fusion between a selectable multidrug resistance (MDR1) cDNA and an adenosine deaminase (ADA) cDNA concomitantly confers multidrug resistance and ADA activity on transfected cells. We have produced a Harvey murine sarcoma virus-derived, replication-defective, recombinant retrovirus to transduce this chimeric MDR-ADA gene efficiently into a great variety of cells. Infection with the MDR-ADA retrovirus conferred the multidrug resistance phenotype on drug-sensitive cells, therefore allowing selection in the presence of colchicine. Colchicine-resistant cells synthesized large amounts of a membrane-associated 210-kDa MDR-ADA fusion protein that preserved both MDR and ADA functional activities. To monitor expression of the chimeric gene in vivo, Kirsten virus-transformed NIH cells were infected with the MDR-ADA retrovirus, and after drug-selection, injected into athymic nude mice. Tumors developed that contained the bifunctionally active MDR-ADA fusion protein. When these mouse tumor cells were placed in tissue culture without the selecting drug, they did not lose the bifunctionally active MDR-ADA fusion protein. The replication-defective, recombinant MDR-ADA retrovirus should be useful to stably introduce the chimeric MDR-ADA gene into a variety of cell types for biological experiments in vitro and in vivo. 相似文献
70.
The partially self-complementary synthetic DNA oligonucleotide d(CG)5T4(CG)5 has been studied by using 1H and 31P NMR and circular dichroism. Results show that, under low-salt conditions (120 mM NaCl buffer), an intramolecular hairpin loop exists in which the double-helical stem region is B-form and the thymidine loop residues have predominantly southern (C2'-endo) sugar conformations. The thymidine glycosidic torsion angles are intermediate between syn and anti or exist as an equilibrium mixture of residues in the two extremes. NOESY data indicate that the structure of the loop region is very similar to that found for d(CG)2T4(CG)2 [Hare, D. R., & Reid, B. R. (1986) Biochemistry 25, 5341-5350]. Under high-salt conditions (6 M NaClO4 buffer), the dominant form (approximately equal to 85%) is an intramolecular hairpin structure in which the stem region forms a Z-form double helix. As in the B-form, the loop thymidine residues are intermediate between the syn and anti conformations or exist as an equilibrium mixture of the two, but the thymidine sugar conformations differ in that they are biased toward northern (C3'-endo) conformations. 相似文献