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1.
Attenuating mutations in glycoproteins E1 and E2 of Sindbis virus produce a highly attenuated strain when combined in vitro. 总被引:14,自引:12,他引:2
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Alterations in either the E1 or the E2 glycoprotein of Sindbis virus can affect pathogenesis in animals. Previously, we identified two distinct E1 glycoprotein gene sequences which differed in their effect on pathogenesis. One had an attenuation phenotype following subcutaneous inoculation of neonatal mice (E1 Ala-72, Gly-75, and Ser-237), while the other was virulent (E1 Val-72, Asp-75, and Ala-237). In this study, we examined the basis for this difference in pathogenesis by using a full-length cDNA clone of Sindbis virus from which infectious RNA could be transcribed in vitro. The relative contribution of each E1 residue to the pathogenesis phenotype was determined by using site-directed mutagenesis to alter each codon individually and in combination. Residues 75 and 237, in combination, appeared to be the major E1 determinants affecting pathogenesis. In addition, the effect of directly combining independently attenuating E1 and E2 mutations in the same virus was examined. The attenuating E1 sequences characterized in this study were coupled to a previously characterized attenuating mutation at E2 residue 114. The resulting recombinant virus, constructed in vitro, exhibited an increased attenuation of neurovirulence as compared with recombinant viruses containing either of the attenuating elements alone. 相似文献
2.
M-Enterococcus medium, used for the detection and enumeration of fecal streptococci from different types of water, demonstrated a very low specificity. We propose the transfer of membrane filters to bile-esculin medium as a confirmation technique. It has proved to be more reliable, faster to perform, and more effective than the random selection of colonies, which is recommended for confirmation in Standard Methods for the Examination of Water and Wastewater (A.E. Greenberg, L.S. Clesceri, and A.D. Eaton, ed., 1992). 相似文献
3.
Anonymous nuclear DNA markers in the American oyster and their implications for the heterozygote deficiency phenomenon in marine bivalves 总被引:4,自引:0,他引:4
A puzzling population-genetic phenomenon widely reported in allozyme
surveys of marine bivalves is the occurrence of heterozygote deficits
relative to Hardy-Weinberg expectations. Possible explanations for this
pattern are categorized with respect to whether the effects should be
confined to protein-level assays or are genomically pervasive and expected
to be registered in both protein- and DNA-level assays. Anonymous nuclear
DNA markers from the American oyster were employed to reexamine the
phenomenon. In assays based on the polymerase chain reaction (PCR), two
DNA-level processes were encountered that can lead to artifactual genotypic
scorings: (a) differential amplification of alleles at a target locus and
(b) amplification from multiple paralogous loci. We describe symptoms of
these complications and prescribe methods that should generally help to
ameliorate them. When artifactual scorings at two anonymous DNA loci in the
American oyster were corrected, Hardy-Weinberg deviations registered in
preliminary population assays decreased to nonsignificant values.
Implications of these findings for the heterozygote-deficit phenomenon in
marine bivalves, and for the general development and use of PCR-based
assays, are discussed.
相似文献
4.
Ventilatory response to isocapnic hyperoxia 总被引:2,自引:0,他引:2
Becker H.; Polo O.; McNamara S. G.; Berthon-Jones M.; Sullivan C. E. 《Journal of applied physiology》1995,78(2):696-701
5.
Stimulation of Brain Pregnenolone Synthesis by Mitochondrial Diazepam Binding Inhibitor Receptor Ligands In Vivo 总被引:2,自引:0,他引:2
A. Korneyev B. S. Pan A. Polo E. Romeo A. Guidotti E. Costa 《Journal of neurochemistry》1993,61(4):1515-1524
Abstract: Evidence that neurosteroids are potent modulators of the action of GABA at GABAA receptors has prompted the investigation of the mechanism that controls brain neurosteroid synthesis by glial cell mitochondria in vivo. In vitro studies suggest that the interaction of the diazepam binding inhibitor (DBI)—a polypeptide that is abundant in steroidogenic cells—with glial mitochondrial DBI receptors (MDRs) is a crucial step in the physiological regulation of neurosteroid biosynthesis. MDRs bind 4-chlorodiazepam (4′-CD), N,N-di-n-hexyl-2-(4-fluorophenyl)-indol-3-acetamide (FGIN-1–27), and the isoquinoline carboxamide PK 11195 with high affinity, and these ligands have been used to investigate whether the stimulation of glial MDRs increases brain pregnenolone production in vivo. Adrenalectomized and castrated (A-C) male rats (to eliminate peripheral sources of pregnenolone) were pretreated with trilostane (to prevent pregnenolone metabolism to progesterone), and the pregnenolone content in brain regions dissected after fixation with a 0.8-s exposure to microwave irradiation focused to the head was determined by HPLC followed by specific radioimmunoassay. The forebrain and cerebellum of A-C rats contained 4–7 ng of pregnenolone/g of tissue, and the olfactory bulb contained 10–14 ng/g. These concentrations of brain pregnenolone are only 30–40% lower than those of shamoperated rats. In contrast, the plasma pregnenolone content of sham-operated rats was 2–3 ng/ml, but it was only 0.15–0.20 ng/ml in the plasma of A-C rats. In A-C rats, treatment with the MDR ligands 4-CD and FGIN-1–27 increased the pregnenolone content in the brain but failed to change the plasma or peripheral tissue content of this steroid. The effect of 4′-CD on brain pregnenolone content was maximal (70–100% increase) at the dose of 18 μmol/kg, 5–10 min after intravenous injection. The effect of oral administration of FGIN-1–27 on brain pregnenolone content was maximal (80–150% increase) at doses of 400–800 μmollkg and peaked at ~ 1 h. That this effect of FGIN-1–27 was mediated by the MDR was documented by pre-treatment with the MDR partial agonist PK 11195 (100 μmol/kg, i.p.). PK 11195 did not affect basal brain pregnenolone content but prevented the accumulation of brain pregnenolone induced by FGIN-1–27. FGIN-1–27 and 4-CD failed to increase the brain concentration of dehydre epiandrosterone in A-C rats. These data suggest that glial cell MDRs play a role in neurosteroid biosynthesis in vivo. 相似文献
6.
Marta Clariano Vanda Marques João Vaz Salma Awam Marta B. Afonso Maria Jesus Perry Cecília MP Rodrigues 《化学与生物多样性》2023,20(3):e202300222
Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile. 相似文献
7.
8.
Water hyacinth Eichhornia crassipes is considered the most damaging aquatic weed in the world. However, few studies have quantified the impact of this weed economically and ecologically, and even fewer studies have quantified the benefits of its control. This paper focuses on water loss saving as the benefit derived from biological control of this plant between 1990 and 2013 at New Year’s Dam, Alicedale, Eastern Cape, South Africa. Estimates of water loss due to evapotranspiration from water hyacinth vary significantly; therefore, the study used three different rates, high, medium and low. A conservative raw agriculture value of R 0.26 per m3 was used to calculate the benefits derived by the water saved. The present benefit and cost values were determined using 10% and 5% discount rates. The benefit/cost ratio at the low evapotranspiration rate was less than one, implying that biological control was not economically viable but, at the higher evapotranspiration rates, the return justified the costs of biological control. However, at the marginal value product of water, the inclusion of the costs of damage to infrastructure, or the adverse effects of water hyacinth on biodiversity, would justify the use of biological control, even at the low transpiration rate. 相似文献
9.
10.
Tadeusz Osadnik Joanna Katarzyna Strzelczyk Rafa? Regu?a Kamil Bujak Martyna Fronczek Ma?gorzata Gonera Marcin Gawlita Jaros?aw Wasilewski Andrzej Lekston Anna Kurek Marek Gierlotka Przemys?aw Trzeciak Micha? Hawranek Zofia Ostrowska Andrzej Wiczkowski Lech Poloński Mariusz G?sior 《PloS one》2016,11(3)