全文获取类型
收费全文 | 695篇 |
免费 | 96篇 |
专业分类
791篇 |
出版年
2021年 | 6篇 |
2018年 | 7篇 |
2016年 | 5篇 |
2015年 | 15篇 |
2014年 | 12篇 |
2013年 | 13篇 |
2012年 | 30篇 |
2011年 | 62篇 |
2010年 | 67篇 |
2009年 | 44篇 |
2008年 | 24篇 |
2007年 | 15篇 |
2006年 | 27篇 |
2005年 | 19篇 |
2004年 | 37篇 |
2003年 | 14篇 |
2002年 | 19篇 |
2001年 | 19篇 |
2000年 | 24篇 |
1999年 | 12篇 |
1998年 | 17篇 |
1997年 | 5篇 |
1995年 | 7篇 |
1994年 | 9篇 |
1993年 | 7篇 |
1992年 | 10篇 |
1991年 | 13篇 |
1990年 | 7篇 |
1989年 | 16篇 |
1988年 | 13篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 9篇 |
1984年 | 11篇 |
1983年 | 11篇 |
1981年 | 8篇 |
1980年 | 10篇 |
1979年 | 15篇 |
1978年 | 12篇 |
1977年 | 10篇 |
1976年 | 6篇 |
1975年 | 8篇 |
1974年 | 7篇 |
1973年 | 10篇 |
1972年 | 11篇 |
1971年 | 9篇 |
1970年 | 11篇 |
1969年 | 10篇 |
1968年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有791条查询结果,搜索用时 15 毫秒
51.
52.
Hao-Han Chang Bernard Choong Anthony RJ Phillips Kerry M Loomes 《Experimental biology and medicine (Maywood, N.J.)》2015,240(1):8-14
Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 µM) and DCI (5 µM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease. 相似文献
53.
Six non-pregnant cows were allocated into 3 groups. Group 1 comprised a pair of lactating cows, whereas groups 2 and 3 each comprised a pair of non-lactating cows. The cows in groups 1 and 2 were dosed intraruminally by stomach tube with zinc oxide at 120 mg Zn per kg of bodyweight at weekly intervals for a period of 33 days. Each cow received a total of 4 doses of zinc oxide. Group 3 served as non-treated control group. Blood samples were collected from all 6 cows daily. Serum was analysed for concentration of calcium. Within 12–24 h of each zinc oxide administration the serum calcium of the lactating cows dropped dramatically indicating the existence of an antagonistic effect between Zn and Ca. The first Zn induced hypocalcaemic episode in the lactating cows was followed by a rise in serum calcium to a level above the pre-dosing level and above the mean value of the control group. The depth of the hypocalcaemic response decreased with the number of zinc oxide dosings. This effect was explained as a response from the stimulation of the calcium homeostatic mechanisms. In the Zn dosed non-lactating cows responses were similar but less clear. The perspective of these findings is discussed in relation to resistance towards parturient hypocalcaemia. 相似文献
54.
55.
W. R. Williams E. J. Eisen J. Nagai H. Bakker 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1978,51(5):249-260
Summary Direct and maternal genetic effects were evaluated for maturing patterns of body weight in mice using a crossfostering design. Crossfostering was performed in one group using dams from populations selected for rapid growth rate (M16 and H6) and their reciprocal F1. crosses. A second crossfostering group consisted of dams from the respective control populations (ICR and C2) and their reciprocal F1. 's. Population differences were partitioned into direct and maternal effects due to genetic origin, correlated selection responses, heterosis and cytoplasmic or sex-linked effects. Degree of maturity was calculated at birth, 12, 21, 31 and 42 days of age by dividing body weight at each age by 63-day weight. Absolute and relative maturing rates were calculated in adjacent age intervals between birth and 63 days. Genetic origin effects (ICR vs. C2; M16 vs. H6) were significant for many maturity traits, with average direct being more important than average maternal genetic effects. In general, correlated responses to selection for maturity traits were larger in the M16 population (M16 vs. ICR) than in the H6 population (H6
vs. C2) and correlated responses in average direct effects were larger than average maternal effects. Positive correlated responses in average direct effects were found for relative maturing rates at all ages and for absolute maturing rates from 31 to 63 days. Apparent correlated responses in degree of maturity were negative for M16 and H6. However, further analysis suggested that the correlated response for degree of maturity in H6 may be positive at later ages and negative at earlier ages. Direct and maternal heterosis for degree of maturity was positive in the selected and control crosses. Absolute and relative maturing rates showed positive heterosis initially, followed by negative heterosis. Reciprocal differences due to the cytoplasm or sex-linkage were not important for patterns of maturity.Paper No. 5244 the Journal Series of the North Carolina Agricultural Experiment Station, Ealeigh, Animal Research Institute Contribution No. 683 and Agricultural University at Wageningen Contribution No. 654–490–12On leave from the Animal Research Institute, Agriculture Canada at Ottawa, OntarioOn leave from the Department of Animal Husbandry, Agricultural University at Wagenitgen, the Netherlands 相似文献
56.
Christopher Phillips Angelique L. Zeringue Jay R. McDonald Seth A. Eisen Prabha Ranganathan 《PloS one》2015,10(11)
The objective of this retrospective cohort study was to determine the effect of tumor necrosis factor inhibitor (TNFi) therapy on the risk of head and neck cancer (HNC) recurrence or HNC-attributable death in patients with rheumatoid arthritis (RA). RA patients with HNC were assembled from the US national Veterans’ Affairs (VA) administrative databases, and diagnoses confirmed and data collected by electronic medical record review. The cohort was divided into those treated with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) versus TNF inhibitors (TNFi) after a diagnosis of HNC. Likelihood of a composite endpoint of recurrence or HNC-attributable death was determined by Cox proportional hazards regression. Of 180 patients with RA and HNC, 31 were treated with TNFi and 149 with nbDMARDs after the diagnosis of HNC. Recurrence or HNC-attributable death occurred in 5/31 (16.1%) patients in the TNFi group and 44/149 (29.5%) patients in the nbDMARD group (p = 0.17); it occurred in 2/16 (13%) patients who received TNFi in the year prior to HNC diagnosis but not after. Overall stage at diagnosis (p = 0.03) and stage 4 HNC (HR 2.49 [CI 1.06–5.89]; p = 0.04) were risk factors for recurrence or HNC-attributable death; treatment with radiation or surgery was associated with a lower risk (HR 0.35 [CI 0.17–0.74]; p = 0.01 and HR 0.39 [CI 0.20–0.76]; p = 0.01 respectively). Treatment with TNFi was not a risk factor for recurrence or HNC-attributable death (HR 0.75; CI 0.31–1.85; p = 0.54). We conclude that treatment with TNFi may be safe in patients with RA and HNC, especially as the time interval between HNC treatment and non-recurrence increases. In this study, TNF inhibition was not associated with an increase in recurrence or HNC-attributable death. 相似文献
57.
Objectives
To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis.Subjects and Methods
A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR.Results
Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4).Conclusion
The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation. 相似文献58.
59.
Interest in the use of low-copy nuclear genes for phylogenetic analyses of
plants has grown rapidly, because highly repetitive genes such as those
commonly used are limited in number. Furthermore, because low- copy genes
are subject to different evolutionary processes than are plastid genes or
highly repetitive nuclear markers, they provide a valuable source of
independent phylogenetic evidence. The gene for granule-bound starch
synthase (GBSSI or waxy) exists in a single copy in nearly all plants
examined so far. Our study of GBSSI had three parts: (1) Amino acid
sequences were compared across a broad taxonomic range, including grasses,
four dicotyledons, and the microbial homologs of GBSSI. Inferred structural
information was used to aid in the alignment of these very divergent
sequences. The informed alignments highlight amino acids that are conserved
across all sequences, and demonstrate that structural motifs can be highly
conserved in spite of marked divergence in amino acid sequence. (2)
Maximum-likelihood (ML) analyses were used to examine exon sequence
evolution throughout grasses. Differences in probabilities among
substitution types and marked among-site rate variation contributed to the
observed pattern of variation. Of the parameters examined in our set of
likelihood models, the inclusion of among-site rate variation following a
gamma distribution caused the greatest improvement in likelihood score. (3)
We performed cladistic parsimony analyses of GBSSI sequences throughout
grasses, within tribes, and within genera to examine the phylogenetic
utility of the gene. Introns provide useful information among very closely
related species, but quickly become difficult to align among more divergent
taxa. Exons are variable enough to provide extensive resolution within the
family, but with low bootstrap support. The combined results of amino acid
sequence comparisons, maximum-likelihood analyses, and phylogenetic studies
underscore factors that might affect phylogenetic reconstruction. In this
case, accommodation of the variable rate of evolution among sites might be
the first step in maximizing the phylogenetic utility of GBSSI.
相似文献
60.
The current view of cytoplasmic RNA-mediated innate immune signaling involves the differential activation of the RNA helicases retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology-2 (LGP2) by distinct RNA viruses. RIG-I, MDA5 and LGP2 form the RIG-I like receptor family (RLR). Since the initial characterization of the RLRs rapid progress has been made in the understanding of the molecular mechanisms that upon virus infection lead to the activation of downstream signaling cascades and the subsequent induction of type I interferon (IFN) and proinflammatory cytokines by these receptors. However, antiviral responses must be tightly regulated in order to prevent uncontrolled production of type I IFN that might have deleterious effects on the host. Exploring the structural and molecular mechanisms that underlie RLR signaling thus was accompanied by the discovery of how RLR-dependent antiviral responses are modulated. This article summarizes the current understanding of endogenous regulation in RLR signaling by various intrinsic molecules that exert their regulatory function in both the steady state or upon viral infection by targeting multiple steps of the signaling cascade. 相似文献