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31.
A mouse genomic clone containing a lactate dehydrogenase-A (LDH-A)
processed pseudogene and a B1 repetitive element was isolated, and a
nucleotide sequence of approximately 3 kb was determined. The pseudogene
and B1 element are flanked by perfect 13-bp repeats, and the B1 sequence
starts at 14 nucleotides 3' to the presumptive polyadenylation signal of
the pseudogene. The nucleotide sequences of the LDH-A genes and processed
pseudogenes from mouse, rat, and human were compared, and a phylogenetic
tree was constructed. The rate and pattern of nucleotide substitutions in
the LDH-A pseudogenes are similar to previously reported results (Li et al.
1984). The average rate of nucleotide substitutions in the LDH-A
pseudogenes is 4.3 X 10(- 9)/site/year. The substitutions of C----T and
G----A are most frequent, and A----G substitutions are relatively high. The
rate of synonymous substitutions in the LDH-A genes is 5.3 X 10(-9), which
is not significantly higher than the average rate of 4.7 X 10(-9) for 35
mammalian genes. The rate of nonsynonymous substitutions in the LDH-A genes
is 0.20 X 10(-9), which is considerably lower than the average rate of 0.88
X 10(-9) for 35 mammalian genes. Thus, the mammalian LDH-A gene appears to
be highly conserved in evolution.
相似文献
32.
The effects of aging on maximal voluntary strength and on the isometric twitch were determined in the ankle dorsiflexor and plantarflexor muscles of 111 healthy men and women aged 20-100 yr. Men were found to be stronger than women at all ages. In both sexes, the average values for maximum voluntary strength of the dorsiflexors and plantarflexors began to decline in the 6th decade. Although the absolute loss of strength was greater for the plantarflexor muscles, the relative losses were similar in the two muscle groups. During maximum voluntary effort, stimulation of motor nerves produced no additional torque in the majority of elderly men and women, indicating that these subjects remained able to utilize their descending motor pathways for optimal muscle activation. Comparisons of muscle compound action potentials, twitch torques, and muscle cross-sectional areas suggested that a decrease in excitable muscle mass was entirely responsible for the lower strength of the elderly. An additional effect of aging was the gradual prolongation of twitch contraction and half-relaxation times throughout the adult life-span. 相似文献
33.
André M Siqueira Lucas I Coutinho Rafael L Gurgel Willian CS Su Luiz M Carvalho Silvana G Benzecry Aline CC Alencar Márcia AA Alexandre Maria Gra?as C Alecrim Marcus VG Lacerda 《Memórias do Instituto Oswaldo Cruz》2014,109(5):540-545
Plasmodium vivax is the most widespread parasite causing malaria, being
especially prevalent in the Americas and Southeast Asia. Children are one of the
most affected populations, especially in highly endemic areas. However, there are
few studies evaluating the therapeutic response of infants with vivax malaria.
This study retrospectively evaluated the parasitaemia clearance in children
diagnosed with vivax malaria during the first five days of exclusive treatment
with chloroquine (CQ). Infants aged less than six months old had a significantly
slower parasitaemia clearance time compared to the group of infants and children
between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon
test; p = 0.004). The impaired clearance of parasitaemia in younger children with
vivax malaria is shown for the first time in Latin America. It is speculated that
CQ pharmacokinetics in young children with vivax malaria is distinct, but this
specific population may also allow the detection of CQ-resistant parasites during
follow-up, due to the lack of previous immunity. 相似文献
34.
Mahaney PE Vu AT McComas CC Zhang P Nogle LM Watts WL Sarkahian A Leventhal L Sullivan NR Uveges AJ Trybulski EJ 《Bioorganic & medicinal chemistry》2006,14(24):8455-8466
Compounds with a combination of norepinephrine and serotonin reuptake inhibition have been approved in the US and Europe for a number of indications, including major depressive disorder and pain disorders such as diabetic neuropathy and fibromyalgia. Efforts to design selective norepinephrine reuptake inhibitors based on SAR from the aryloxypropanamine series of monoamine reuptake inhibitors have led to the identification of a potent new class of dual acting norepinephrine and serotonin reuptake inhibitors, namely the 3-(1H-indol-1-yl)-3-arylpropan-1-amines. 相似文献
35.
Background
Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.Methods and Findings
We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors.Conclusions
Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis. Please see later in the article for the Editors'' Summary 相似文献36.
37.
Casey McComas Jeffrey Cohen Christine Huselton Michael Marella Edward Melenski Cheryl Mugford Ov Slayden Richard Winneker Jay Wrobel Matthew R. Yudt Andrew Fensome 《Bioorganic & medicinal chemistry letters》2012,22(23):7119-7122
We have developed a new series of progesterone receptor modulators based upon the 4-aryl-phenylsulfonamide. Initial work in the series afforded potent compounds with good properties, however an advanced intermediate proved to be genotoxic in a non-GLP Ames assay following metabolic activation. We subsequently solved this problem and identified advanced leads which demonstrated oral efficacy in rhesus monkey pharmacodynamic and kinetics models. 相似文献
38.
39.
Erickson SD Banner B Berthel S Conde-Knape K Falcioni F Hakimi I Hennessy B Kester RF Kim K Ma C McComas W Mennona F Mischke S Orzechowski L Qian Y Salari H Tengi J Thakkar K Taub R Tilley JW Wang H 《Bioorganic & medicinal chemistry letters》2008,18(4):1402-1406
This paper describes the lead optimization of a new series of potent, selective, orally bioavailable, brain-penetrant MCH-1 receptor antagonists. A major focus of the work was to achieve a selectivity profile appropriate for in vivo efficacy studies and safety. 相似文献
40.
McComas CC Vu AT Mahaney PE Cohn ST Fensome A Marella MA Nogle L Trybulski EJ Ye F Zhang P Alfinito P Bray J Johnston G Koury E Deecher DC 《Bioorganic & medicinal chemistry letters》2008,18(18):4929-4931
Norepinephrine and serotonin play an important role in a wide variety of biological processes and are implicated in a number of neurological disorders. A novel class of 1-(3-amino-1-phenylpropyl)indolin-2-ones was designed and synthesized that displays potent norepinephrine reuptake inhibition while maintaining high selectivity (>100-fold) against the human serotonin and dopamine transporters. 相似文献