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961.
The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis 总被引:4,自引:1,他引:3
Ying Yuan YaQi Zhu Deborah D. Crane & Clifton E. Barry III 《Molecular microbiology》1998,29(6):1449-1458
There are three major structural classes of mycolic acids in the cell envelope of Mycobacterium tuberculosis (MTB): alpha-, methoxy- and ketomycolate. The two oxygen-containing classes are biosynthetically related through a common α-methyl hydroxymycolate intermediate. BCG strains that fail to produce methoxymycolate and instead produce only keto- and alpha-mycolic acids show apparent defects in the O -methyltransferase MMAS-3. Overproduction of MMAS-3 from MTB resulted in a complete replacement of ketomycolate by methoxymycolate in both BCG and MTB. In vitro growth of these recombinant strains lacking ketomycolate was impaired at reduced temperatures but appeared to be normal at 37°C. Glucose uptake was significantly decreased in such strains, but uptake of chenodeoxycholate and glycine was unaffected. Although sensitivity to INH remained unchanged, these cells were found to be hypersensitive to ampicillin and rifampicin. Infectivity of BCG and H37Rv wild type or MMAS-3 overproducers in THP-1 cells was somewhat affected, but the ability of the strains lacking ketomycolate to grow within this macrophage-like cell line was severely compromised. In vivo labelling of mycolic acids during growth of H37Rv within THP-1 cells revealed a substantial increase in ketomycolate and alphamycolate synthesized by intracellularly grown mycobacteria. These results establish a critical role for mycolate composition in proper cell wall function during the growth of MTB in vivo . 相似文献
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Finn J. Hawkins Shingo Suzuki Mary Lou Beermann Cristina Barillà Ruobing Wang Carlos Villacorta-Martin Andrew Berical J.C. Jean Jake Le Suer Taylor Matte Chantelle Simone-Roach Yang Tang Thorsten M. Schlaeger Ana M. Crane Nadine Matthias Sarah X.L. Huang Scott H. Randell Joshua Wu Darrell N. Kotton 《Cell Stem Cell》2021,28(1):79-95.e8
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964.
M.A. Maxwell P.V. Nelson S.J. Chin B.C. Paton W.F. Carey D.I. Crane 《Human genetics》1999,105(1-2):38-44
Peroxisome biogenesis disorders are a heterogeneous group of human neurodegenerative diseases caused by peroxisomal metabolic
dysfunction. At the molecular level, these disorders arise from mutations in PEX genes that encode proteins required for the import of proteins into the peroxisomal lumen. The Zellweger syndrome spectrum
of diseases is a major sub-set of these disorders and represents a clinical continuum from Zellweger syndrome (the most severe)
through neonatal adrenoleukodystrophy to infantile Refsum disease. The PEX1 gene, which encodes a cytoplasmic AAA ATPase, is the responsible gene in more than half of the Zellweger syndrome spectrum
patients, and mutations in PEX1 can account for the full spectrum of phenotypes seen in these patients. In these studies, we have undertaken mutation analysis
of PEX1 in skin fibroblast cell lines from Australasian Zellweger syndrome spectrum patients. A previously reported common PEX1 mutation that gives rise to a G843D substitution and correlates with the less severe disease phenotypes has been found to
be present at high frequency in our patient cohort. We also report a novel PEX1 mutation that occurs at high frequency in Zellweger syndrome spectrum patients. This mutation produces a frameshift in exon 13,
a change that leads to the premature truncation of the PEX1 protein. A Zellweger syndrome patient who was homozygous for this
mutation and who survived for less than two months from birth had undetectable levels of PEX1 mRNA. This new common mutation
therefore correlates with a severe disease phenotype. We have adopted procedures for the detection of this mutation for successful
prenatal diagnosis.
Electronic Publication 相似文献
965.
Kevin D Donohue Dharshan C Medonza Eli R Crane Bruce F O'Hara 《Biomedical engineering online》2008,7(1):14
This work presents a non-invasive high-throughput system for automatically detecting characteristic behaviours in mice over
extended periods of time, useful for phenotyping experiments. The system classifies time intervals on the order of 2 to 4
seconds as corresponding to motions consistent with either active wake or inactivity associated with sleep. A single Polyvinylidine
Difluoride (PVDF) sensor on the cage floor generates signals from motion resulting in pressure. This paper develops a linear
classifier based on robust features extracted from normalized power spectra and autocorrelation functions, as well as novel
features from the collapsed average (autocorrelation of complex spectrum), which characterize transient and periodic properties
of the signal envelope. Performance is analyzed through an experiment comparing results from direct human observation and
classification of the different behaviours with an automatic classifier used in conjunction with this system. Experimental
results from over 28.5 hours of data from 4 mice indicate a 94% classification rate relative to the human observations. Examples
of sequential classifications (2 second increments) over transition regions between sleep and wake behaviour are also presented
to demonstrate robust performance to signal variation and explain performance limitations. 相似文献
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Summary Bothras and the transplasma membrane electron transport system have been implicated in the control of cell growth. Since the loss of growth regulation is at the heart of the cancerous phenotype, we have investigated the effect of factors like antitumor drugs, which inhibit cell growth, and growth factors which either cause or prepare the cells for growth. We have found that growth factors increase the plasma membrane electron transport of the normal cells but not that of the cells which have been transfected with oncogenicras (which have a 2–5-fold faster basal rate). In the presence of adriamycin the activity of the electron transport system is and cell numbers are decreased more in normal cells than in the cells which have been transfected with the oncogenic version of the Harveyras gene. Cisplatin inhibits cell growth but does not inhibit ferricyanide reduction. Ferricyanide alone or in conjunction with EGF or TPA does not stimulate cell proliferation with either cell line in the absence of fetal calf serum, so simple activation of plasma membrane electron transport is not sufficient to activate a complete growth response.Abbreviations EGF
epidermal growth factor
- TPA
phorbol myristate acetate
- PDGF
platelet derived growth factor
- MTT
3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromides
- SDS
sodium dodecyl sulfate 相似文献
970.
M A Miller M Yousuf P S Griffin M Bartlett J K Crane 《Microbiology and immunology》1979,23(10):955-964
Synergistic antibiotic studies were undertaken to compare the effectiveness of two new beta-lactamase resistant cephalosporins, cefamandole, and carbenicillin, with four aminoglycosides against clinical strains of Serratia marcescens. The strains demonstrated various combinations of resistance and/or susceptibility to the antibiotics tested. Tobramycin was the most effective aminoglycoside when used in combination with beta-lactam antibiotics. Carbenicillin and cefamandole demonstrated similar activity with aminoglycosides in synergy experiments. Tobramycin-carbenicillin was found to be the superior pairs as indicated by the total number of strains inhibited. This combination was the only one effective against certain high drug resistant strains and the strain resistant to all four aminoglycosides. Carbenicillin or cefamandole with tobramycin exhibited comparable activity against multiple drug resistant organisms. However, mutants significantly more resistant to cefamandole developed during susceptibility testing. The findings of this study have clinical relevance for treating infections by this formidable pathogen. 相似文献