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81.
Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene. 总被引:10,自引:3,他引:7
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G Slupphaug F H Markussen L C Olsen R Aasland N Aarsaether O Bakke H E Krokan D E Helland 《Nucleic acids research》1993,21(11):2579-2584
Recent cloning of a cDNA (UNG15) encoding human uracil-DNA glycosylase (UDG), indicated that the gene product of M(r) = 33,800 contains an N-terminal sequence of 77 amino acids not present in the presumed mature form of M(r) = 25,800. This led to the hypothesis that the N-terminal sequence might be involved in intracellular targeting. To examine this hypothesis, we analysed UDG from nuclei, mitochondria and cytosol by western blotting and high resolution gel filtration. An antibody that recognises a sequence in the mature form of the UNG protein detected all three forms, indicating that they are products of the same gene. The nuclear and mitochondrial form had an apparent M(r) = 27,500 and the cytosolic form an apparent M(r) = 38,000 by western blotting. Gel filtration gave essentially similar estimates. An antibody with specificity towards the presequence recognised the cytosolic form of M(r) = 38,000 only, indicating that the difference in size is due to the presequence. Immunofluorescence studies of HeLa cells clearly demonstrated that the major part of the UDG activity was localised in the nuclei. Transfection experiments with plasmids carrying full-length UNG15 cDNA or a truncated form of UNG15 encoding the presumed mature UNG protein demonstrated that the UNG presequence mediated sorting to the mitochondria, whereas UNG lacking the presequence was translocated to the nuclei. We conclude that the same gene encodes nuclear and mitochondrial uracil-DNA glycosylase and that the signals for mitochondrial translocation resides in the presequence, whereas signals for nuclear import are within the mature protein. 相似文献
82.
Bellur Seetharam James E. Bakke David H. Alpers 《Biochemical and biophysical research communications》1983,115(1):238-244
The rat ileal brush border membrane binds both free [125I]-intrinsic factor (IF) and the IF-[57Co]cobalamin (cbl) complex. This binding is observed with IF isolated from rat stomach, but not from IF isolated from hog, canine and human stomachs. The binding of rat-IF[57Co]cbl can be blocked with free rat IF but not with hog IF. The IF-cbl complex binds at a higher affinity (Ka=0.15 × 109 M?1) compared to that of free IF (Ka=0.9 × 109 M?1). Rat IF-cbl also binds efficiently to human and canine ileal membranes. While antibody to the canine ileal receptor blocks the binding of rat, human or hog IF-[57Co]cbl to human and canine ileal membranes, it does not affect the binding of rat IF-[57Co]cbl to rat ileal membranes. These findings demostrate that the rat ileal receptor is different from canine and human ileal receptors. 相似文献
83.
R K Berge A Aarsland O M Bakke M Farstad 《The International journal of biochemistry》1983,15(2):191-204
1. The activities of acyl-CoA hydrolase, catalase, urate oxidase and peroxisomal palmitoyl-CoA oxidation as well as the protein content and the level of CoASH and long-chain acyl-CoA were measured in subcellular fractions of liver from rats fed diets containing phenobarbital (0.1% w/w) or clofibrate (0.3% w/w). 2. Whereas phenobarbital administration resulted in increased microsomal protein, the clofibrate-induced increase was almost entirely attributed to the mitochondrial fraction with minor contribution from the light mitochondrial fraction. 3. The specific activity of palmitoyl-CoA hydrolase in the microsomal fraction was only slightly affected while the mitochondrial enzyme was increased to a marked extent (3-4-fold) by clofibrate. 4. Phenobarbital administration mainly enhanced the microsomal palmitoyl-CoA hydrolase. 5. The increased long-chain acyl-CoA and CoASH level observed after clofibrate treatment was mainly associated with the mitochondrial, light mitochondrial and cytosolic fractions, while the slight increase in the levels of these compounds found after phenobarbital feeding was largely of microsomal origin. 6. The findings suggest that there is an intraperoxisomal CoASH and long-chain acyl-CoA pool. 7. The specific activity of palmitoyl-CoA hydrolase, catalase and peroxisomal palmitoyl-CoA oxidation was increased in the lipid-rich floating layer of the cytosol-fraction. 8. The changes distribution of the peroxisomal marker enzymes and microsomal palmitoyl-CoA hydrolase after treatment with hypolipidemic drugs may be related to the origin of peroxisomes. 相似文献
84.
T A Bakke 《Zeitschrift für Parasitenkunde (Berlin, Germany)》1978,55(2):153-164
The anatomical and morphological variability of sporocysts and metacercariae of Leucochloridium sp. recovered from natural infected Succinea pfeifferi Rossm?ssler collected in the Agdenes area. Norway (63 degrees 35'N, 9 degrees 45'E), was studied by light microscopy. The results are compared with five species from the Nearctic and Palearctic with known adult stage (L. variae McIntosh, 1932; L. fuscostriatum Robinson, 1947; L. perturbatum Pojmanska, 1969; L. subtilis Pojmanska, 1969; L. fuscum Rietschel, 1970) and nine species with unknown adult stage. In the larval stages no morphological taxonomical characters were found to separate Leucochloridium sp. as a species distinct from the five (and nine) species. The variability and validity of the characters used is discussed. 相似文献
85.
Amit Kaura Adam Hartley Vasileios Panoulas Ben Glampson Anoop S. V. Shah Jim Davies Abdulrahim Mulla Kerrie Woods Joe Omigie Anoop D. Shah Mark R. Thursz Paul Elliott Harry Hemmingway Bryan Williams Folkert W. Asselbergs Michael OSullivan Graham M. Lord Adam Trickey Jonathan AC Sterne Dorian O. Haskard Narbeh Melikian Darrel P. Francis Wolfgang Koenig Ajay M. Shah Rajesh Kharbanda Divaka Perera Riyaz S. Patel Keith M. Channon Jamil Mayet Ramzi Khamis 《PLoS medicine》2022,19(2)
BackgroundThere is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS.Methods and findingsWe conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin.Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor.ConclusionsThese multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation.Trial registrationClinicalTrials.gov - Amit Kaura and colleagues investigate whether mildly elevated high sensitivity C-reactive protein is associated with mortality risk in patients with suspected acute coronary syndromes. NCT03507309相似文献
86.
Kristine Bakke Westergaard Magni Olsen Kyrkjeeide Marie Kristine Brandrud 《Ecology and evolution》2021,11(23):17117
There is a growing demand for ecological restoration using suitable seeds following international standards or national legal demands for local seed‐sourcing. However, before selecting the appropriate geographic origin of seeds, it is vital to explore taxonomic complexity related to the focal taxa. We used ddRAD‐seq to screen genomic diversity within Carex bigelowii s.lat. focussing on Norway. This species complex is considered a candidate for seeding, but presents considerable morphological, ecological, and genetic variation. The genetic structure of 132 individuals of C. bigelowii s.lat., including Carex nigra as an outgroup, was explored using ordinations, clustering analyses, and a genetic barrier algorithm. Two highly divergent clusters were evident, supporting the recognition of two taxonomic units “C. dacica” and C. bigelowii “subsp. bigelowii”. Previously defined seed‐sourcing regions for C. bigelowii s.lat. did not consider the known taxonomic complexity, and therefore interpreted the overall genetic structure as seed‐sourcing regions, not taxa. We estimated genetic neighborhood sizes within each taxon to be 100–150 km and 300 km, respectively, indicating species‐specific delimitations of local seed‐sourcing regions. Frequent hybrids, local genetic distinctiveness, and suggested ecotypes add complexity to the discussed seed‐sourcing regions. Our results show how genomic screening of diversity and structure in a species complex can alleviate the taxonomic impediment, inform practical questions, and legal requirements related to seed‐sourcing, and together with traditional taxonomic work provide necessary information for a sound management of biodiversity. 相似文献
87.
Kristine Bakke Westergaard Marte Holten Jørgensen Tove M. Gabrielsen Inger Greve Alsos Christian Brochmann 《Journal of Biogeography》2010,37(7):1262-1276
Aim The oceanic Saxifraga rivularis L. presents one of the most extreme disjunctions known in the arctic flora: it has a small amphi‐Beringian range and a larger amphi‐Atlantic one. It was recently suggested to have had a single allopolyploid origin in Beringia at least one glacial cycle ago, followed by gradual expansion in a more humid period and differentiation into two allopatric subspecies (the Atlantic ssp. rivularis and the Beringian ssp. arctolitoralis). Here we explore the history of its extreme disjunction. Location The amphi‐Beringian and northern amphi‐Atlantic regions. Methods We obtained amplified fragment length polymorphisms (AFLPs) and chloroplast DNA sequences from 36 populations (287 individuals) and 13 populations (15 individuals), respectively. The data were analysed using principal coordinates analyses, Bayesian clustering methods, and analyses of molecular variance. Results Two distinctly divergent AFLP groups were observed, corresponding to the two described subspecies, but, surprisingly, four of the West Atlantic populations belonged to the supposedly Beringian endemic ssp. arctolitoralis. This was confirmed by re‐examination of their morphological characteristics. The overall AFLP diversity in the species was low (26.4% polymorphic markers), and there was no variation in the five investigated chloroplast DNA (cpDNA) regions. There was little geographic structuring of the AFLP diversity within each subspecies, even across the extreme disjunction in ssp. arctolitoralis, across the Bering Sea, and across the Atlantic Ocean, except that most plants from the arctic Svalbard archipelago formed a separate genetic group with relatively high diversity. Main conclusions The extreme disjunction in S. rivularis has evidently formed at least twice. The first expansion from Beringia was followed by allopatric differentiation into one Beringian and one Atlantic subspecies, which are distinctly divergent at AFLP loci but still harbour identical cpDNA haplotypes, suggesting that the expansion was quite recent but before the last glaciation. The next expansion from Beringia probably occurred by means of several long‐distance dispersals in the current interglacial, resulting in the colonization of the western Atlantic region by ssp. arctolitoralis. The poor geographic structuring within each subspecies suggests frequent long‐distance dispersals from two main Weichselian refugia, one Beringian and one western‐central European, but it is possible that the genetic group in Svalbard originates from an additional refugium. 相似文献
88.
89.
Øynebråten I Barois N Hagelsteen K Johansen FE Bakke O Haraldsen G 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(8):5358-5369
We have recently shown that several proinflammatory chemokines can be stored in secretory granules of endothelial cells (ECs). Subsequent regulated exocytosis of such chemokines may then enable rapid recruitment of leukocytes to inflammatory sites. Although IL-8/CXCL8 and eotaxin-3/CCL26 are sorted to the rod-shaped Weibel-Palade body (WPB), we found that GROalpha/CXCL1 and MCP-1/CCL2 reside in small granules that, similarly to the WPB, respond to secretagogue stimuli. In the present study, we report that GROalpha and MCP-1 colocalized in 50- to 100-nm granules, which occur throughout the cytoplasm and at the cell cortex. Immunofluorescence confocal microscopy revealed no colocalization with multimerin or tissue plasminogen activator, i.e., proteins that are released from small granules of ECs by regulated exocytosis. Moreover, the GROalpha/MCP-1-containing granules were Rab27-negative, contrasting the Rab27-positive, WPB. The secretagogues PMA, histamine, and forskolin triggered distinct dose and time-dependent responses of GROalpha release. Furthermore, GROalpha release was more sensitive than IL-8 release to inhibitors and activators of PKA and PKC but not to an activator of Epac, a cAMP-regulated GTPase exchange factor, indicating that GROalpha release is regulated by molecular adaptors different from those regulating exocytosis of the WPB. On the basis of these findings, we designated the GROalpha/MCP-1-containing compartment the type 2 granule of regulated secretion in ECs, considering the WPB the type 1 compartment. In conclusion, we propose that the GROalpha/MCP-1-containing type 2 granule shows preferential responsiveness to important mediators of EC activation, pointing to the existence of selective agonists that would allow differential release of selected chemokines. 相似文献
90.