全文获取类型
收费全文 | 124篇 |
免费 | 5篇 |
出版年
2021年 | 2篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2016年 | 1篇 |
2015年 | 6篇 |
2014年 | 4篇 |
2013年 | 4篇 |
2012年 | 4篇 |
2011年 | 4篇 |
2010年 | 5篇 |
2009年 | 2篇 |
2008年 | 4篇 |
2007年 | 10篇 |
2006年 | 5篇 |
2005年 | 8篇 |
2004年 | 7篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2001年 | 8篇 |
2000年 | 1篇 |
1999年 | 6篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1937年 | 2篇 |
排序方式: 共有129条查询结果,搜索用时 15 毫秒
11.
Miriam YH Ueda Paulo G Alvarenga Juliana M Real Eloisa de Sá Moreira Aripuan? Watanabe Ana Maria Passos-Castilho Matheus Vescovi Yana Novis Vanderson Rocha Adriana Seber Jose SR Oliveira Celso A Rodrigues Celso FH Granato 《Memórias do Instituto Oswaldo Cruz》2015,110(4):461-467
Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem
cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and
early diagnosis of related clinical diseases, constitute essential measures to
improve outcomes. A prospective survey on the incidence and clinical features of
HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the
impact of this infection on HSCT outcome remains unclear. A rapid test based on
real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen
and quantify clinical samples for HHV-6. The detection step was based on reaction
with TaqMan® hydrolysis probes. A set of previously described primers and
probes have been tested to evaluate efficiency, sensitivity and reproducibility. The
target efficiency range was 91.4% with linearity ranging from 10-106
copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of
plasma. The qPCR assay developed in the present study was simple, rapid and
sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this
test may be useful as a practical tool to help elucidate the clinical relevance of
HHV-6 infection and reactivation in different scenarios and to determine the need for
surveillance. 相似文献
12.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献13.
14.
Woolford LB Southgate TD Margison GP Milsom MD Fairbairn LJ 《The journal of gene medicine》2006,8(1):29-34
The O(6)-methylguanine-DNA-methyltransferase (MGMT) inactivator O(6)-benzylguanine (O(6)-beG) is currently under clinical investigation as a potential tumour-sensitising agent. In clinical trials its use has been associated with increased myelotoxicity and a reduced maximum tolerated dose (MTD) for BCNU. Thus the concept of myeloprotection by gene therapy with an O(6)-beG-insensitive mutant of MGMT is soon to be tested. Recently, an alternative inactivator has been described (O(6)-(4-bromothenyl)guanine, PaTrin-2), which shows potential advantages over O(6)-beG in terms of higher activity against wild-type MGMT and oral formulation. The use of PaTrin-2 has also been associated with increased myelotoxicity in clinical trials and thus PaTrin-2 may also be a candidate for use in conjunction with mutant MGMT gene transfer in genetic chemoprotective strategies. However, its activity against mutant MGMTs has not been reported. We show here that the P(140)K mutant of MGMT is highly resistant to inactivation by PaTrin-2. Furthermore, we show that a human haemopoietic cell line (K562) transduced with a retroviral vector encoding MGMT(P140K) is highly resistant to the cytotoxic effects of PaTrin-2 in combination with the methylating agent temozolomide, and that cells expressing MGMT(P140K) can be effectively enriched in vitro following challenge with this drug combination. Finally, we show that animals reconstituted with bone marrow expressing MGMT(P140K) exhibit haemopoietic resistance to PaTrin-2/temozolomide, which results in in vivo selection of gene-modified cells. All of these effects were comparable to those also achieved using O(6)-beG/temozolomide. Thus our data show that MGMT(P140K) is a suitable candidate for chemoprotective gene therapy where PaTrin-2 is being used in conjunction with temozolomide. 相似文献
15.
Tattersall GJ de Andrade DV Brito SP Abe AS Milsom WK 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2006,176(2):125-138
In order to study the relative roles of receptors in the upper airways, lungs and systemic circulation in modulating the ventilatory
response of caiman (Caiman latirostris) to inhaled CO2, gas mixtures of varying concentrations of CO2 were administered to animals breathing through an intact respiratory system, via a tracheal cannula by-passing the upper
airways (before and after vagotomy), or via a cannula delivering gas to the upper airways alone. While increasing levels of
hypercarbia led to a progressive increase in tidal volume in animals with intact respiratory systems (Series I), breathing
frequency did not change until the CO2 level reached 7%, at which time it decreased. Despite this, at the higher levels of hypercarbia, the net effect was a large
and progressive increase in total ventilation. There were no associated changes in heart rate or arterial blood pressure.
On return to air, there was an immediate change in breathing pattern; breathing frequency increased above air-breathing values,
roughly to the same maximum level regardless of the level of CO2 the animal had been previously breathing, and tidal volume returned rapidly toward resting (baseline) values. Total ventilation
slowly returned to air breathing values. Administration of CO2 via different routes indicated that inhaled CO2 acted at both upper airway and pulmonary CO2-sensitive receptors to modify breathing pattern without inhibiting breathing overall. Our data suggest that in caiman, high
levels of inspired CO2 promote slow, deep breathing. This will decrease dead-space ventilation and may reduce stratification in the saccular portions
of the lung. 相似文献
16.
David C Zappulla Arindel SR Maharaj Jessica J Connelly Rebecca A Jockusch Rolf Sternglanz 《BMC molecular biology》2006,7(1):40-12
Background
By screening a plasmid library for proteins that could cause silencing when targeted to the HMR locus in Saccharomyces cerevisiae, we previously reported the identification of Rtt107/Esc4 based on its ability to establish silent chromatin. In this study we aimed to determine the mechanism of Rtt107/Esc4 targeted silencing and also learn more about its biological functions. 相似文献17.
Alternaria alternata is a common fungal parasite on fruits and other plants and produces a number of mycotoxins, including alternariol (3,7,9-trihydroxy-1-methyl-6H-dibenzo [b,d]pyran-6-one), alternariol monomethyl ether (3,7-dihydroxy-9-methoxy-1-methyl-6H-dibenzo[b,d]pyran-6-one), and the mutagen altertoxin I {[1S-(1α,12aβ,12bα)] 1,2,11,12,12a, 12b-hexahydro-1,4,9,12a-tetrahydroxy-3,10-perylenedione}.
Alternariol and alternariol monomethyl ether have previously been detected in some samples of fruit beverages. Stability studies
of these toxins as well as altertoxin I added to fruit juices and wine (10–100 ng/mL) were carried out. To include altertoxin
I in the analysis, cleanup with a polymer-based Varian Abselut solid phase extraction column was used, as recoveries from
C-18 columns were low. The stabilities of alternariol and alternariol monomethyl ether in a low acid apple juice containing
no declared vitamin C were compared with those in the same juice containing added vitamin C (60 mg/175 ml); there were no
apparent losses at room temperature over 20 days or at 80°C after 20 min. in either juice. Altertoxin I was moderately stable
in pH 3 buffer (75% remaining after a two week period). Furthermore, altertoxin I was stable or moderately stable in three
brands of apple juice tested over 1–27 day periods and in a sample of red grape juice over 7 days. It is concluded that altertoxin
I is sufficiently stable to be found in fruit juices and should be included in methods for alternariol and alternariol monomethyl
ether. 相似文献
18.
Abstract: The dynamics of newly established elk (Cervus elaphus) populations can provide insights about maximum sustainable rates of reproduction, survival, and increase. However, data used to estimate rates of increase typically have been limited to counts and rarely have included complementary estimates of vital rates. Complexities of population dynamics cannot be understood without considering population processes as well as population states. We estimated pregnancy rates, survival rates, age ratios, and sex ratios for reintroduced elk at Theodore Roosevelt National Park, North Dakota, USA; combined vital rates in a population projection model; and compared model projections with observed elk numbers and population ratios. Pregnancy rates in January (early in the second trimester of pregnancy) averaged 54.1% (SE = 5.4%) for subadults and 91.0% (SE = 1.7%) for adults, and 91.6% of pregnancies resulted in recruitment at 8 months. Annual survival rates of adult females averaged 0.96 (95% CI = 0.94-0.98) with hunting included and 0.99 (95% CI = 0.97-0.99) with hunting excluded from calculations. Our fitted model explained 99.8% of past variation in population estimates and represents a useful new tool for short-term management planning. Although we found no evidence of temporal variation in vital rates, variation in population composition caused substantial variation in projected rates of increase (Λ = 1.20-1.36). Restoring documented hunter harvests and removals of elk by the National Park Service led to a potential rate of Λ = 1.26. Greater rates of increase substantiated elsewhere were within the expected range of chance variation, given our model and estimates of vital rates. Rates of increase realized by small elk populations are too variable to support inferences about habitat quality or density dependence. 相似文献
19.
We examined the magnitude of the hypoxic metabolic response in golden-mantled ground squirrels to determine whether the shift in thermoregulatory set point (T(set)) and subsequent fall in body temperature (T(b)) and metabolic rate observed in small mammals were greater in a species that routinely experiences hypoxic burrows and hibernates. We measured the effects of changing ambient temperature (T(a); 6--29 degrees C) on metabolism (O(2) consumption and CO(2) production), T(b), ventilation, and heart rate in normoxia and hypoxia (7% O(2)). The magnitude of the hypoxia-induced falls in T(b) and metabolism of the squirrels was larger than that of other rodents. Metabolic rate was not simply suppressed but was regulated to assist the initial fall in T(b) and then acted to slow this fall and stabilize T(b) at a new, lower level. When T(a) was reduced during 7% O(2), animals were able to maintain or elevate their metabolic rates, suggesting that O(2) was not limiting. The slope of the relationship between temperature-corrected O(2) consumption and T(a) extrapolated to a T(set) in hypoxia equals the actual T(b). The data suggest that T(set) was proportionately related to T(a) in hypoxia and that there was a shift from increasing ventilation to increasing O(2) extraction as the primary strategy employed to meet increasing metabolic demands under hypoxia. The animals were neither hypothermic nor hypometabolic, as T(b) and metabolic rate appeared to be tightly regulated at new but lower levels as a result of a coordinated hypoxic metabolic response. 相似文献
20.