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Inhibitor studies of the only known eukaryotic methionyl-tRNA transformylase (10-formyltetrahydrofolate:L-methionyl-tRNA N-transformylase, EC 2.1.2.9) were carried out. All the natural pteroylglutamic acid derivatives examined, with the exception of pteroylglutamic acid, are inhibitors. The most effective is 5-methyltetrahydrofolate (5-CH3-H4PteGlu) (KI = 3 . 10(-6) M), which is the only noncompetitive inhibitor of the enzyme. All the other derivatives tested are competitive, and H4PteGlu shows a cooperative inhibition. These and other data obtained with pteroylglutamic analogues show that, in contrast to the bacterial enzyme, Euglena transformylase is also inhibited by compounds without a fully reduced pyrazine ring and is very sensitive to compounds with a methyl group in position 5 or 10 of the pteridine ring. 相似文献
134.
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
135.
Burba I Colombo GI Staszewsky LI De Simone M Devanna P Nanni S Avitabile D Molla F Cosentino S Russo I De Angelis N Soldo A Biondi A Gambini E Gaetano C Farsetti A Pompilio G Latini R Capogrossi MC Pesce M 《PloS one》2011,6(7):e22158
Background
Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs), have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of “enhancement” strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit.Principal Findings
Pharmacologic inhibition of histone deacetylases (HDACs) is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34+ were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction.Conclusions
Our results show that HDAC blockade leads to phenotype changes in CD34+ cells with enhanced self renewal and cardioprotection. 相似文献136.
137.
Here we study maximum running speed (MRS) limitations on a previously proposed model of energetic and muscle-tendon unit functions on running mammals. In the present work the MRS and some anatomical or physiological limitations are estimated for mammals with body mass between 1.5 and 300 kg. The MRS variations with body mass are discussed and compared with results of previous experimental and observational studies. The tendon strength seems to be the most relevant limitation, but leg extensor muscle mass and metabolic costs could be relevant also. The physiological maximum muscle speed seems to be less important in the body mass range studied here. 相似文献
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139.
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
140.