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101.
102.
We have studied the functional effects of extracellular Cd(2+) on human ether-a-go-go-related gene (HERG) encoded K(+) channels. Low concentrations (10-200 &mgr;M) of extracellular Cd(2+) increased outward currents through HERG channels; 200 &mgr;M Cd(2+) more than doubled HERG currents and altered current kinetics. Cd(2+) concentrations up to 200 &mgr;M did not change the voltage dependence of channel activation, but shifted the voltage dependence of inactivation to more depolarized membrane potentials. Cd(2+) concentrations >/=500 &mgr;M shifted the voltage dependence of channel activation to more positive potentials. These results are consistent with a somewhat specific ability of Cd(2+) to destabilize the inactivated state. We tested the hypothesis that channel inactivation is essential for Cd(2+)-induced increases in HERG K(+) currents, using a double point mutation (G628C/S631C) that diminishes HERG inactivation (Smith, P. L., T. Baukrowitz, and G. Yellen. 1996. Nature (Lond.). 379:833-836). This inactivation-removed mutant is insensitive to low concentrations of Cd(2+). Thus, Cd(2+) had two distinct effects on HERG K(+) channels. Low concentrations of Cd(2+) caused relatively selective effects on inactivation, resulting in a reduction of the apparent rectification of the channel and thereby increasing HERG K(+) currents. Higher Cd(2+) concentrations affected activation gating as well, possibly by a surface charge screening mechanism or by association with a lower affinity site. 相似文献
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105.
Y Novik LM Ryan DG Haller R Asbury JP Dutcher A Schutt 《Cancer immunology, immunotherapy : CII》1999,16(4):261-266
The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma.
Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium.
The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with
a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m2 were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for
the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete
response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable
for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates
and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer. 相似文献
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108.
Expression of N-linked sialyl Le(x) determinants and O-glycans in the carbohydrate moiety of human amniotic fluid transferrin during pregnancy 总被引:3,自引:0,他引:3
Transferrin, a glycoprotein involved in iron transport in body fluids, was
isolated from amniotic fluid of a hydramniospatient by sequential
anion-exchange chromatography and gel filtration. The N-glycans of human
amniotic fluid transferrin (hAFT) were enzymatically liberated by PNGase-F
digestion, isolated by gel filtration and fractionated by (high-pH)
anion-exchange chromatography. After alkaline borohydride treatment of
native hAFT, the released O-glycans were isolated by gel filtration and
fractionated by anion-exchange chroma-tography. Structure elucidation of 14
N- and 2 O-glycans was performed by 500 or 600 MHz1H-NMR spectroscopy.
Besides conventional N-glycans established earlier for human serum
transferrin (hST), new (alpha1-3)-fucosylated N- glycans were found,
representing sialyl Le(x) elements. Furthermore, as compared to hST, a
higher degree of (alpha1-6)-fucosylation and an increase in branching from
di- to triantennary compounds has been detected. The presence of O-glycans
is demonstrated for the first time in transferrin.
相似文献
109.
Evolutionary transfer of ORF-containing group I introns between different subcellular compartments (chloroplast and mitochondrion) 总被引:10,自引:2,他引:8
Turmel M; Cote V; Otis C; Mercier JP; Gray MW; Lonergan KM; Lemieux C 《Molecular biology and evolution》1995,12(4):533-545
We describe here a case of homologous introns containing homologous open
reading frames (ORFs) that are inserted at the same site in the large
subunit (LSU) rRNA gene of different organelles in distantly related
organisms. We show that the chloroplast LSU rRNA gene of the green alga
Chlamydomonas pallidostigmatica contains a group I intron (CpLSU.2)
encoding a site-specific endonuclease (I-CpaI). This intron is inserted at
the identical site (corresponding to position 1931-1932 of the Escherichia
coli 23S rRNA sequence) as a group I intron (AcLSU.m1) in the mitochondrial
LSU rRNA gene of the amoeboid protozoon Acanthamoeba castellanii. The
CpLSU.2 intron displays a remarkable degree of nucleotide similarity in
both primary sequence and secondary structure to the AcLSU.m1 intron;
moreover, the Acanthamoeba intron contains an ORF in the same location
within its secondary structure as the CpLSU.2 ORF and shares with it a
strikingly high level of amino acid similarity (65%; 42% identity). A
comprehensive survey of intron distribution at site 1931 of the chloroplast
LSU rRNA gene reveals a rather restricted occurrence within the
polyphyletic genus Chlamydomonas, with no evidence of this intron among a
number of non- Chlamydomonad green algae surveyed, nor in land plants. A
parallel survey of homologues of a previously described and similar
intron/ORF pair (C. reinhardtii chloroplast CrLSU/A. castellanii
mitochondrial AcLSU.m3) also shows a restricted occurrence of this intron
(site 2593) among chloroplasts, although the intron distribution is
somewhat broader than that observed at site 1931, with site-2593 introns
appearing in several green algal branches outside of the Chlamydomonas
lineage. The available data, while not definitive, are most consistent with
a relatively recent horizontal transfer of both site-1931 and site- 2593
introns (and their contained ORFs) between the chloroplast of a
Chlamydomonas-type organism and the mitochondrion of an Acanthamoeba- like
organism, probably in the direction chloroplast to mitochondrion. The data
also suggest that both introns could have been acquired in a single event.
相似文献
110.
The robustness of two phylogenetic methods: four-taxon simulations reveal a slight superiority of maximum likelihood over neighbor joining 总被引:6,自引:3,他引:3
The robustness (sensitivity to violation of assumptions) of the maximum-
likelihood and neighbor-joining methods was examined using simulation.
Maximum likelihood and neighbor joining were implemented with Jukes-
Cantor, Kimura, and gamma models of DNA substitution. Simulations were
performed in which the assumptions of the methods were violated to varying
degrees on three model four-taxon trees. The performance of the methods was
evaluated with respect to ability to correctly estimate the unrooted
four-taxon tree. Maximum likelihood outperformed neighbor joining in 29 of
the 36 cases in which the assumptions of both methods were satisfied. In
133 of 180 of the simulations in which the assumptions of the
maximum-likelihood and neighbor-joining methods were violated, maximum
likelihood outperformed neighbor joining. These results are consistent with
a general superiority of maximum likelihood over neighbor joining under
comparable conditions. They extend and clarify an earlier study that found
an advantage for neighbor joining over maximum likelihood for
gamma-distributed mutation rates.
相似文献