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11.
Gabriel von Euler Ingeborg van der Ploeg Bertil B. Fredholm Kjell Fuxe 《Journal of neurochemistry》1991,56(1):178-183
To examine whether GTP-binding proteins (G proteins) mediate the ability of neurotensin to lower the affinity of dopamine D2 agonist binding, the modulation by neurotensin in vitro of N-[3H]propylnorapomorphine [( 3H]-NPA) binding was investigated following pretreatment with pertussis toxin and N-ethylmaleimide in rat neostriatal membranes. Preincubation with N-ethylmaleimide (100 microM) markedly inhibited pertussis toxin-induced back-ADP ribosylation of three proteins with apparent molecular masses of 41, 40, and 39 kDa, respectively. This inhibition was prevented by adding dithiothreitol (250 microM) during the preincubation. N-Ethylmaleimide increased the KD (180 +/- 30%) and decreased the Bmax (-31 +/- 9%) of [3H]NPA binding sites but did not affect the binding properties of the selective D2 antagonist [3H]raclopride. N-Ethylmaleimide pretreatment did not affect the neurotensin (3 nM)-induced increase in the KD of [3H]NPA binding sites. Pertussin toxin treatment in vivo and in vitro was similarly ineffective. In conclusion, the present study indicates that neurotensin modulation of D2 agonist binding in neostriatal membranes is not mediated by G proteins. 相似文献
12.
Klaus Lange Konrad Keller Wolf-Dieter Ludwig Ingrid Monden Ingeborg Reinsch Ursula Brandt 《Journal of neurochemistry》1982,39(6):1594-1600
Previous studies have revealed two different kinds of regulation of glucose utilization in cell lines derived from the nervous system (Keller et al., 1981). We found glucose metabolism of C-6 glioma cells to be limited and regulated by membrane transport. In contrast, glucose utilization of C-1300 neuroblastoma (N2A) cells was limited by the known regulatory enzymes of the Embden-Meyerhof pathway. Under the given experimental conditions the "membrane-limited" C-6 glioma cells were characterized by periodically changing glucose transport rates and very low intracellular glucose concentrations, which remained constant in spite of widely differing transport rates. These findings suggest the close functional coupling between transport and phosphorylation required for the regulation of glucose transport by cellular metabolic needs. 相似文献
13.
Feulgen-DNA contents and chromosome lengths and projected areas were measured in salivary gland nuclei from Drosophila prepupae which had developed at 25° or 15° C. Nuclei from a given prepupa fell into 3 to 5 DNA classes corresponding to different levels of polyteny. The 15° nuclei tended to fall into higher classes than those from 25°-reared animals, and their chromosomes were, on average, about 50% wider. Chromosomes within a given DNA class did not differ significantly in mean area, length or width between the temperature groups, and slight apparent differences in mean DNA content were attributable to systematic microdensitometric errors associated with differences in the spreading behaviour of the nuclei. On cytological examination, chromosomes from the two temperature groups differed mainly in width and stain intensity, but some other differences in appearance could not be accounted for by levels of polyteny. The mean length of the chromosome complement was about 400 m. From one polytenic level to the next the chromosomes increased by about 10% in length, 40% in width and 17% in mean absorbance. The DNA content approximately doubled; small apparent deviations from the 12 ratio could have been due to microdensitometric error or to underreplication of heterochromatin. 相似文献
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15.
Ohne Zusammenfassung 相似文献
16.
Ingeborg A. Brouwer Johanna M. Geleijnse Veronique M. Klaasen Liesbeth A. Smit Erik J. Giltay Janette de Goede Annemieke C. Heijboer Daan Kromhout Martijn B. Katan 《PloS one》2013,8(12)
Background
Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer.Methods
The Alpha Omega Trial (ClinicalTrials.gov Identifier: ) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60–80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL). NCT00127452Findings
Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: −0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84–1.58).Interpretation
An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from −0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.Trial registration information
ClinicalTrials.gov; Identifier: . URL: http://www.clinicaltrials.gov/ct2/show/ NCT00127452. NCT00127452相似文献17.
Rob J. Van Geest Ingeborg Klaassen Sarit Y. Lesnik-Oberstein H. Stevie Tan Marco Mura Roel Goldschmeding Cornelis J. F. Van Noorden Reinier O. Schlingemann 《Journal of cell communication and signaling》2013,7(1):1-9
In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and CCN2 (connective tissue growth factor; CTGF) cause blindness by neovascularization and subsequent fibrosis. This angio-fibrotic switch is associated with a shift in the balance between vitreous levels of CCN2 and VEGF in the eye. Here, we investigated the possible involvement of other important mediators of fibrosis, tissue inhibitor of metalloproteinases (TIMP)-1 and transforming growth factor (TGF)-β2, and of the matrix metalloproteinases (MMP)-2 and MMP-9, in the natural course of PDR. TIMP-1, activated TGF-β2, CCN2 and VEGF levels were measured by ELISA in 78 vitreous samples of patients with PDR (n = 28), diabetic patients without PDR (n = 24), and patients with the diabetes-unrelated retinal conditions macular hole (n = 10) or macular pucker (n = 16), and were related to MMP-2 and MMP-9 activity on zymograms and to clinical data, including degree of intra-ocular neovascularization and fibrosis. TIMP-1, CCN2 and VEGF levels, but not activated TGF-β2 levels, were significantly increased in the vitreous of diabetic patients, with the highest levels in PDR patients. CCN2 and the CCN2/VEGF ratio were the strongest predictors of degree of fibrosis. In diabetic patients with or without PDR, activated TGF-β2 levels correlated with TIMP-1 levels, whereas in PDR patients, TIMP-1 levels, MMP-2 and proMMP-9 were associated with degree of neovascularization, like VEGF levels, but not with fibrosis. We confirm here our previous findings that retinal fibrosis in PDR patients is significantly correlated with vitreous CCN2 levels and the CCN2/VEGF ratio. In contrast, TIMP-1, MMP-2 and MMP-9 appear to have a role in the angiogenic phase rather than in the fibrotic phase of PDR. 相似文献
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19.
Marcus J. G.W. Ladds Gergana Popova Andrs Pastor-Fernndez Srinivasaraghavan Kannan Ingeborg M.M. van Leeuwen Maria Hkansson Bjrn Walse Fredrik Tholander Ravi Bhatia Chandra S. Verma David P. Lane Sonia Laín 《The Journal of biological chemistry》2020,295(52):17935
The tenovins are a frequently studied class of compounds capable of inhibiting sirtuin activity, which is thought to result in increased acetylation and protection of the tumor suppressor p53 from degradation. However, as we and other laboratories have shown previously, certain tenovins are also capable of inhibiting autophagic flux, demonstrating the ability of these compounds to engage with more than one target. In this study, we present two additional mechanisms by which tenovins are able to activate p53 and kill tumor cells in culture. These mechanisms are the inhibition of a key enzyme of the de novo pyrimidine synthesis pathway, dihydroorotate dehydrogenase (DHODH), and the blockage of uridine transport into cells. These findings hold a 3-fold significance: first, we demonstrate that tenovins, and perhaps other compounds that activate p53, may activate p53 by more than one mechanism; second, that work previously conducted with certain tenovins as SirT1 inhibitors should additionally be viewed through the lens of DHODH inhibition as this is a major contributor to the mechanism of action of the most widely used tenovins; and finally, that small changes in the structure of a small molecule can lead to a dramatic change in the target profile of the molecule even when the phenotypic readout remains static. 相似文献
20.
Anne E. Bjune Ingeborg Helvik H. John B. Birks 《Vegetation History and Archaeobotany》2013,22(3):215-229
The origin and developmental history of Fagus sylvatica forests in south-eastern Norway have been studied through pollen analysis and AMS radiocarbon-dating of peat from two small forest hollows. In this area F. sylvatica appears to have a long history, from the first occurrence of F. sylvatica pollen at ca. 9100 cal. b.p. to its local expansion ca. 1300–1200 cal. b.p. At this time a shift from a diverse landscape mosaic with many plant taxa present, including broad-leaved trees, to a less diverse landscape mosaic with Picea abies and F. sylvatica trees is interpreted from the pollen data. The long history of F. sylvatica suggests that the existing forests are not recent plantations, but implies that these forests are native. The presence of pollen indicative of anthropogenic activity combined with charcoal before the expansion of F. sylvatica, as well as comparison with data from nearby sites, suggest that the forest development was likely to be a result of human activity and climatic changes, particularly changes in moisture conditions. 相似文献