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101.
The frequencies of A, C, G, and T in mitochondrial DNA vary among species due to unequal rates of mutation between the bases.
The frequencies of bases at fourfold degenerate sites respond directly to mutation pressure. At first and second positions,
selection reduces the degree of frequency variation. Using a simple evolutionary model, we show that first position sites
are less constrained by selection than second position sites and, therefore, that the frequencies of bases at first position
are more responsive to mutation pressure than those at second position. We define a measure of distance between amino acids
that is dependent on eight measured physical properties and a similarity measure that is the inverse of this distance. Columns
1, 2, 3, and 4 of the genetic code correspond to codons with U, C, A, and G in their second position, respectively. The similarity
of amino acids in the four columns decreases systematically from column 1 to column 2 to column 3 to column 4. We then show
that the responsiveness of first position bases to mutation pressure is dependent on the second position base and follows
the same decreasing trend through the four columns. Again, this shows the correlation between physical properties and responsiveness.
We determine a proximity measure for each amino acid, which is the average similarity between an amino acid and all others
that are accessible via single point mutations in the mitochondrial genetic code structure. We also define a responsiveness
for each amino acid, which measures how rapidly an amino acid frequency changes as a result of mutation pressure acting on
the base frequencies. We show that there is a strong correlation between responsiveness and proximity, and that both these
quantities are also correlated with the mutability of amino acids estimated from the mtREV substitution rate matrix. We also
consider the variation of base frequencies between strands and between genes on a strand. These trends are consistent with
the patterns expected from analysis of the variation among genomes.
[Reviewing Editor: Dr. David Pollock] 相似文献
102.
Effects of zinc ex vivo and intracellular zinc chelator in vivo on taurine uptake in goldfish retina
Taurine and zinc exert neurotrophic effects. Zinc modulates Na+/Cl−-dependent transporters. This study examined the effect of zinc (ZnSO4) ex vivo and zinc chelator N,N,N′,N′-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN) in vivo on [3H]taurine transport in goldfish retina. The effect of TPEN in vivo on taurine and zinc levels was determined. Isolated cells
were incubated in Ringer with zinc (0.1–100 μM). Taurine transport was done with taurine (0.001–1 mM) and 50 nM [3H]taurine. Zinc (100 μM) noncompetitively inhibited taurine transport. TPEN was administered intraocularly and retinas extracted
3, 5 and 10 days later. Taurine was determined by HPLC (nmol/mg protein) and zinc by spectrophotometry ICP (mg/mg protein).
Taurine and zinc levels decreased at 3 days and increased at 10 days after TPEN administration. At 10 days after intraocular
TPEN, taurine transport affinity increased (K
s = 0.018 ± 0.006 vs. 0.028 ± 0.008 mM). Apparently, zinc deficiency affects the taurine–zinc complex and taurine availability.
The increased taurine uptake affinity by TPEN was possibly associated with a response to maximize retinal taurine content
at low zinc concentration. 相似文献
103.
Joyce JBC van Beers Annemiek Willemze Jeroen J Jansen Gerard HM Engbers Martin Salden Jos Raats Jan W Drijfhout Annette HM van der Helm-van Mil Rene EM Toes Ger JM Pruijn 《Arthritis research & therapy》2013,15(5):R140
Introduction
Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients.Methods
Twenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip.Results
Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations.Conclusions
Compared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores. 相似文献104.
105.
Urbina P Collado MI Alonso A Goñi FM Flores-Díaz M Alape-Girón A Ruysschaert JM Lensink MF 《Biochimica et biophysica acta》2011,1808(10):2618-2627
Clostridium perfringens phospholipase C (CpPLC), also called α-toxin, is the main virulence factor for gas gangrene in humans. The lipase activity serves the bacterium to generate lipid signals in the host eukaryotic cell, and ultimately to degrade the host cell membranes. Several previous reports indicated that CpPLC was specific for phosphatidylcholine and sphingomyelin. Molecular docking studies described in this paper predict favorable interactions of the CpPLC active site with other phospholipids, e.g. phosphatidylethanolamine, phosphatidylinositol and, to a lesser extent, phosphatidylglycerol. On the basis of these predictions, we have performed experimental studies showing α-toxin to degrade all the phospholipids mentioned above. The molecular docking data also provide an explanation for the observed lower activity of CpPCL on sphingomyelin as compared to the glycerophospholipids. 相似文献
106.
Lívia de Figueiredo Diniz Julio A. Urbina Isabel Mayer de Andrade Ana Lia Mazzeti Tassiane Assíria F. Martins Ivo Santana Caldas André Talvani Isabela Ribeiro Maria Terezinha Bahia 《PLoS neglected tropical diseases》2013,7(8)
Background
Current chemotherapy for Chagas disease is unsatisfactory due to its limited efficacy, particularly in the chronic phase, with frequent side effects that can lead to treatment discontinuation. Combined therapy is envisioned as an ideal approach since it may improve treatment efficacy whilst decreasing toxicity and the likelihood of resistance development. We evaluated the efficacy of posaconazole in combination with benznidazole on Trypanosoma cruzi infection in vivo.Methods and Findings
Benznidazole and posaconazole were administered individually or in combination in an experimental acute murine infection model. Using a rapid treatment protocol for 7 days, the combined treatments were more efficacious in reducing parasitemia levels than the drugs given alone, with the effects most evident in combinations of sub-optimal doses of the drugs. Subsequently, the curative action of these drug combinations was investigated, using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or concomitantly for 20 days. The effects of the combination treatments on parasitological cures were higher than the sum of such effects when the drugs were administered separately at the same doses, indicating synergistic activity. Finally, sequential therapy experiments were carried out with benznidazole or posaconazole over a short interval (10 days), followed by the second drug administered for the same period of time. It was found that the sequence of benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates comparable to those obtained with the full (20 days) treatments with either drug alone, and no cure was observed for the short treatments with drugs given alone.Conclusions
Our data demonstrate the importance of investigating the potential beneficial effects of combination treatments with marketed compounds, and showed that combinations of benznidazole with posaconazole have a positive interaction in murine models of Chagas disease. 相似文献107.
Raúl Esperante Leonard Brand Kevin E. Nick Orlando Poma Mario Urbina 《Palaeogeography, Palaeoclimatology, Palaeoecology》2008,257(3):344-360
Fossil baleen is rare in the sedimentary record. This paper documents the exceptional occurrence of thirty seven fossil whale specimens with preserved baleen in the Neogene Pisco Formation during a transect survey in a limited area west of the Ica River Valley near the town of Ocucaje in southern Peru. The sedimentary layers consist of tuffaceous and diatomaceous sandstones, diatomaceous mudstones, and dolomites, deposited in a shallow marine embayment. Observations of modern whale carcasses on the seafloor and stranded individuals indicate that baleen detaches from the mouth of the whales very rapidly after death, and that bones deteriorate very rapidly as a result of scavenging activity and abrasion. In contrast, the bones of the Pisco Formation whales are exceptionally well preserved, and their baleen is often found in life position suspended from the rostrum. Sedimentary structures found associated with some skeletons indicate tidal and storm processes, suggesting that the environment was not anoxic. This exceptional occurrence of fossil baleen suggests early mineralization of the baleen attachment to the rostrum or rapid burial of the skeletons before any detachment or loss could occur. 相似文献
108.
Background
Interferon-α in combination with ribavirin is the current gold standard for treatment of chronic hepatitis C. It is unknown if the development of autoimmune thyroid disease (TD) during treatment confers an improved chance of achieving sustained virologic response. The aim of this study is to assess the chance of achieving sustained virologic response (SVR) in patients who developed TD during treatment when compared with those who did not.Methods
We performed a tertiary hospital-based retrospective nested case-control analysis of 19 patients treated for hepatitis C who developed thyroid disease, and 76 controls (matched for age, weight, gender, cirrhosis and aminotransferase levels) who did not develop TD during treatment. Multivariate logistic-regression models were used to compare cases and controls.Results
The development of TD was associated with a high likelihood of achieving SVR (odds ratio, 6.0; 95% confidence interval, 1.5 to 24.6) for the pooled group containing all genotypes. The likelihood of achieving SVR was increased in individuals with genotype 1 HCV infection who developed TD (odds ratio, 5.2; 95% confidence interval, 1.2 to 22.3), and all genotype 3 patients who developed TD achieved SVR.Conclusions
Development of TD during treatment for hepatitis C infection is associated with a significantly increased chance of achieving SVR. The pathophysiogical mechanisms for this observation remain to be determined.Trial Registration
The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRB12610000830099 相似文献109.
Many of the known xylose-fermenting (X-F) yeasts are placed in the Scheffersomyces clade, a group of ascomycete yeasts that have been isolated from plant tissues and in association with lignicolous insects. We formally recognize fourteen species in this clade based on a maximum likelihood (ML) phylogenetic analysis using a multilocus dataset. This clade is divided into three subclades, each of which exhibits the biochemical ability to ferment cellobiose or xylose. New combinations are made for seven species of Candida in the clade, and three X-F taxa associated with rotted hardwood are described: Scheffersomyces illinoinensis (type strain NRRL Y-48827(T) = CBS 12624), Scheffersomyces quercinus (type strain NRRL Y-48825(T) = CBS 12625), and Scheffersomyces virginianus (type strain NRRL Y-48822(T) = CBS 12626). The new X-F species are distinctive based on their position in the multilocus phylogenetic analysis and biochemical and morphological characters. The molecular characterization of xylose reductase (XR) indicates that the regions surrounding the conserved domain contain mutations that may enhance the performance of the enzyme in X-F yeasts. The phylogenetic reconstruction using XYL1 or RPB1 was identical to the multilocus analysis, and these loci have potential for rapid identification of cryptic species in this clade. 相似文献
110.
WalterDuartedeAraujo Filho Fábio Kurt Schneider Rigoberto EM Morales 《Biomedical engineering online》2012,11(1):1-14