全文获取类型
收费全文 | 71篇 |
免费 | 4篇 |
专业分类
75篇 |
出版年
2021年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2015年 | 2篇 |
2014年 | 3篇 |
2013年 | 9篇 |
2012年 | 1篇 |
2011年 | 3篇 |
2010年 | 3篇 |
2009年 | 1篇 |
2008年 | 2篇 |
2007年 | 1篇 |
2006年 | 1篇 |
2005年 | 3篇 |
2004年 | 1篇 |
2003年 | 2篇 |
2002年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 4篇 |
1977年 | 1篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 3篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有75条查询结果,搜索用时 15 毫秒
51.
F A Kimball S E Porteus K T Kirton R D Frielink D M Creasy A D Dayan 《Prostaglandins》1979,18(3):377-385
Intravenous injection of 600 microgram PGE2 or PGI2 significantly increased serum LH and prolactin levels in estradiol treated ovariectomized rats. There was no effect on serum FSH concentration. PGE2 and PGI2 stimulated LH release in a non-dose dependent manner, while prolactin levels were positively correlated with the dose administered following PGI2 treatment. 6-keto-PGF1 alpha at a comparable dose had no effect on pituitary hormone levels. Subcutaneous administration of 1 mg/kg or 60 mg/kg PGI2 for seven days significantly depressed serum LH level both in male and female rats. These doses had no effect on serum FSH or prolactin levels. 相似文献
52.
Monophyly of the order Rodentia inferred from mitochondrial DNA sequences of the genes for 12S rRNA, 16S rRNA, and tRNA-valine 总被引:1,自引:2,他引:1
A recent analysis of amino acid sequence data (Graur et al.) suggested that
the mammalian order Rodentia is polyphyletic, in contrast to most
morphological data, which support rodent monophyly. At issue is whether the
hystricognath rodents, such as the guinea pig, represent an independent
evolutionary lineage within mammals, separate from the sciurognath rodents.
To resolve this problem, we sequenced a region (2,645 bp) of the
mitochondrial genome of the guinea pig containing the complete 12S
ribosomal RNA, 16S ribosomal RNA, and transfer RNA(VAL) genes for
comparison with the available sciurognath and other mammalian sequences.
Several methods of analysis and statistical tests of the data all show
strong support for rodent monophyly (91%-98% bootstrap probability, or BP).
Calibration with the mammalian fossil record suggests a Cretaceous date
(107 mya) for the divergence of sciurognaths and hystricognaths. An older
date (38 mya) for the controversial Mus- Rattus divergence also is
supported by these data. Our neighbor-joining analyses of all available
sequence data (25 genes) confirm that some individual genes support rodent
polyphyly but that tandem analysis of all data does not. We propose that
the conflicting results are due to several compounding factors. The unique
biochemical properties of some hystricognath metabolic proteins, largely
responsible for generating this controversy, may have a single explanation:
a cascade effect resulting from inactivation of the zinc-binding abilities
of insulin. After excluding six genes possibly affected by insulin
inactivation, analyses of all available sequence data (7,117 nucleotide
sites, 3,099 amino acid sites) resulted in strong support for rodent
monophyly (94% BP for DNA sequences, 90% for protein sequences), which
lends support to the insulin-cascade hypothesis.
相似文献
53.
Post ‘omic’ era has resulted in the development of many primary, secondary and derived databases. Many analytical and
visualization bioinformatics tools have been developed to manage and analyze the data available through large sequencing
projects. Availability of heterogeneous databases and tools make it difficult for researchers to access information from varied
sources and run different bioinformatics tools to get desired analysis done. Building integrated bioinformatics platforms is one of
the most challenging tasks that bioinformatics community is facing. Integration of various databases, tools and algorithm is a
challenging problem to deal with. This article describes the bioinformatics analysis workflow management systems that are
developed in the area of gene sequence analysis and phylogeny. This article will be useful for biotechnologists, molecular
biologists, computer scientists and statisticians engaged in computational biology and bioinformatics research. 相似文献
54.
Thomas D Walko III Valentina Di Caro Jon Piganelli Timothy R Billiar Robert SB Clark Rajesh K Aneja 《Molecular medicine (Cambridge, Mass.)》2014,20(1):612-624
Pathophysiological conditions that lead to the release of the prototypic damage-associated molecular pattern molecule high mobility group box 1 (HMGB1) also result in activation of poly(ADP-ribose) polymerase 1 (PARP1; now known as ADP-ribosyl transferase 1 [ARTD1]). Persistent activation of PARP1 promotes energy failure and cell death. The role of poly(ADP-ribosyl)ation in HMGB1 release has been explored previously; however, PARP1 is a versatile enzyme and performs several other functions including cross-talk with another nicotinamide adenine dinucleotide- (NAD+) dependent member of the Class III histone deacetylases (HDACs), sirtuin-1 (SIRT1). Previously, it has been shown that the hyperacetylation of HMGB1 is a seminal event prior to its secretion, a process that also is dependent on HDACs. Therefore, in this study, we seek to determine if PARP1 inhibition alters LPS-mediated HMGB1 hyperacetylation and subsequent secretion due to its effect on SIRT1. We demonstrate in an in vitro model that LPS treatment leads to hyperacetylated HMGB1 with concomitant reduction in nuclear HDAC activity. Treatment with PARP1 inhibitors mitigates the LPS-mediated reduction in nuclear HDAC activity and decreases HMGB1 acetylation. By utilizing an NAD+-based mechanism, PARP1 inhibition increases the activity of SIRT1. Consequently, there is an increased nuclear retention and decreased extracellular secretion of HMGB1. We also demonstrate that PARP1 physically interacts with SIRT1. Further confirmation of this data was obtained in a murine model of sepsis, that is, administration of PJ-34, a specific PARP1 inhibitor, led to decreased serum HMGB1 concentrations in mice subjected to cecal ligation and puncture (CLP) as compared with untreated mice. In conclusion, our study provides new insights in understanding the molecular mechanisms of HMGB1 secretion in sepsis. 相似文献
55.
Termites of the genus Odontotermes are important decomposers in the Old World tropics and are sometimes important pests of crops, timber and trees. The species within the genus often have overlapping size ranges and are difficult to differentiate based on morphology. As a result, the taxonomy of Odontotermes in Peninsular Malaysia has not been adequately worked out. In this study, we examined the phylogeny of 40 samples of Odontotermes from Peninsular Malaysia using two mitochondrial DNA regions, that is, the 16S ribosomal RNA and cytochrome oxidase subunit I genes, to aid in elucidating the number of species in the peninsula. Phylogenies were reconstructed from the individual gene and combined gene data sets using parsimony and likelihood criteria. The phylogenies supported the presence of up to eleven species in Peninsular Malaysia, which were identified as O. escherichi, O. hainanensis, O. javanicus, O. longignathus, O. malaccensis, O. oblongatus, O. paraoblongatus, O. sarawakensis, and three possibly new species. Additionally, some of our taxa are thought to comprise a complex of two or more species. The number of species found in this study using DNA methods was more than the initial nine species thought to occur in Peninsular Malaysia. The support values for the clades and morphology of the soldiers provided further evidence for the existence of eleven or more species. Higher resolution genetic markers such as microsatellites would be required to confirm the presence of cryptic species in some taxa. 相似文献
56.
Herbert SB Baraf Michael A Becker Sergio R Gutierrez-Urena Edward L Treadwell Janitzia Vazquez-Mellado Claudia D Rehrig Faith D Ottery John S Sundy Robert A Yood 《Arthritis research & therapy》2013,15(5):R137
Introduction
Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.Methods
Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.Results
Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than nonresponders (30/93; 32%).Conclusions
Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.Trial registrations
, NCT00325195 NCT01356498相似文献57.
58.
K T Kirton R J Ericsson J A Ray A D Forbes 《Journal of reproduction and fertility》1970,21(2):275-278
59.
Frances A. Kimball Kenneth T. Kirton Lillian J. Wyngarden 《Prostaglandins & other lipid mediators》1975,10(6):853-864
Myometrial low speed supernatant prepared from non-pregnant rhesus uteri was incubated with 3H-Prostaglandin (PG) E1 with or without addition of unlabelled prostaglandins. The uptake of 3H-PGE1 was inhibited in a dose dependent fashion by PGE2>PGE1>PGA1>PGF2=PGA1>PGB1=PGB2≥PGD2. PGE1 metabolites inhibited 3H-PGE1 binding in the following order: 13,14-dihydro-PGE1>13,14-dihydro-15-keto-PGE1=15-keto-PGE1. The specific binding of 3H-PGE1 and 3H-PGF2 was similarly affected by the temperature and time of incubation. Equilibrium binding constants determined using rhesus uteri obtained during the luteal phase of the menstrual cycle indicate the presence of high affinity PGE1 binding sites with an average (n=3) apparent dissociation constant of 2.2 × 10−9M and a lower affinity PGE1 binding site with a Kd 1 × 10−8M. No high affinity — low capacity 3H-PGF2 sites could be demonstrated.
Relative uterine stimulating potencies of some natural prostaglandins and prostaglandin analogs tested after acute intravenous administration in mid-pregnant rhesus monkeys corresponded with the PGE1 binding inhibition of the respective compound. The uterine stimulating potencies of the prostaglandin analogs tested were: (15S)-15-methyl-PGE2=16,16-dimethyl-PGE2>17-phenyl-18,19,20-trinor-P GE2>16 phenoxy-17,18,19,20-tetranor-PGE2=PGE2=PGE1=(15S)-15-methyl-PGE2>PGF2. 相似文献
60.
INTRODUCTIONAsearlyasin1948wehavefr8CtionatedisolatednucleifromnormalandtumorcellsbyextractionwithiMNaCIanddilutealkali[1].Thenuclearresiduewasthenstudiedmorethoroughly[2,3].Lateron,sillillarproteinousnuclearresidueswereisolatedbyotherworkers[46]andasstud… 相似文献