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131.
The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC) molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO) is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC) as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000-7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10-100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells. 相似文献
132.
Saldanha JF Carrero JJ Lobo JC Stockler-Pinto MB Leal VO Calixto A Geloneze B Mafra D 《Regulatory peptides》2012,173(1-3):82-85
Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia. 相似文献
133.
Background
Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. 相似文献134.
135.
Charles D Criscione Claudia LL Valentim Hirohisa Hirai Philip T LoVerde Timothy JC Anderson 《Genome biology》2009,10(6):R71-13
Background
Schistosoma mansoni is a blood fluke that infects approximately 90 million people. The complete life cycle of this parasite can be maintained in the laboratory, making this one of the few experimentally tractable human helminth infections, and a rich literature reveals heritable variation in important biomedical traits such as virulence, host-specificity, transmission and drug resistance. However, there is a current lack of tools needed to study S. mansoni's molecular, quantitative, and population genetics. Our goal was to construct a genetic linkage map for S. mansoni, and thus provide a new resource that will help stimulate research on this neglected pathogen. 相似文献136.
Fluorescence recovery after photobleaching (FRAP) is an experimental technique used to measure the mobility of proteins within
the cell nucleus. After proteins of interest are fluorescently tagged for their visualization and monitoring, a small region
of the nucleus is photobleached. The experimental FRAP data are obtained by recording the recovery of the fluorescence in
this region over time.
In this paper, we characterize the fluorescence recovery curves for diffusing nuclear proteins undergoing binding events with
an approximate spatially homogeneous structure. We analyze two mathematical models for interpreting the experimental FRAP
data, namely a reaction-diffusionmodel and a compartmental model. Perturbation analysis leads to a clear explanation of two
important limiting dynamical types of behavior exhibited by experimental recovery curves, namely, (1) a reduced diffusive
recovery, and (2) a biphasic recovery characterized by a fast phase and a slow phase. We show how the two models, describing
the same type of dynamics using different approaches, relate and share common ground. The results can be used to interpret
experimental FRAP data in terms of protein dynamics and to simplify the task of parameter estimation. Application of the results
is demonstrated for nuclear actin and type H1 histone. 相似文献
137.
Ciriza I Carrero P Azcoitia I Lundeen SG Garcia-Segura LM 《Journal of neurobiology》2004,61(2):209-221
Neuroprotective effects of estradiol are well characterized in animal experimental models. However, in humans, the outcome of estrogen treatment for cognitive function and neurological diseases is very controversial. Selective estrogen receptor modulators (SERMs) may represent an alternative to estrogen for the treatment or the prevention of neurodegenerative disorders. SERMs interact with the estrogen receptors and have tissue-specific effects distinct from those of estradiol, acting as estrogen agonists in some tissues and as antagonists in others. In this study we have assessed the effect of tamoxifen, raloxifene, lasofoxifene (CP-336,156), bazedoxifene (TSE-424), and 17beta-estradiol on the hippocampus of adult ovariectomized rats, after the administration of the excitotoxin kainic acid. Administration of kainic acid induced the expression of vimentin in reactive astroglia and a significant neuronal loss in the hilus. SERMs did not affect vimentin immunoreactivity in the hilus, while 17beta-estradiol significantly reduced the surface density of vimentin immunoreactive profiles. Estradiol, tamoxifen (0.4-2 mg/kg), raloxifene (0.4-2 mg/kg), and bazedoxifene (2 mg/kg) prevented neuronal loss in the hilus after the administration of kainic acid. Lasofoxifene (0.4-2 mg/kg) was not neuroprotective. These findings indicate that SERMs present different dose-dependent neuroprotective effects. Furthermore, the mechanisms of neuroprotection by SERMs and estradiol are not identical, because SERMs do not significantly affect reactive gliosis while neuroprotection by estradiol is associated with a strong down-regulation of reactive astroglia. 相似文献
138.
Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion 总被引:32,自引:4,他引:28
Simple but exact statistical tests for detecting a cluster of associated
nucleotide changes in DNA are presented. The tests are based on the linear
distribution of a set of s sites among a total of n sites, where the s
sites may be the variable sites, sites of insertion/deletion, or
categorized in some other way. These tests are especially useful for
detecting gene conversion and intragenic recombination in a sample of DNA
sequences. In this case, the sites of interest are those that correspond to
particular ways of splitting the sequences into two groups (e.g., sequences
A and D vs. sequences B, C, and E-J). Each such split is termed a
phylogenetic partition. Application of these methods to a well-documented
case of gene conversion in human gamma-globin genes shows that sites
corresponding to two of the three observed partitions are significantly
clustered, whereas application to hominoid mitochondrial DNA
sequences--among which no recombination is expected to occur--shows no
evidence of such clustering. This indicates that clustering of
partition-specific sites is largely due to intragenic recombination or gene
conversion. Alternative hypotheses explaining the observed clustering of
sites, such as biased selection or mutation, are discussed.
相似文献
139.
The nucleotide sequences of the cow epsilon 2 and epsilon 4 globin genes
were determined. The sequences were 95% identical. These genes arose via a
four-gene block duplication that also gave rise to the bovine fetal (gamma)
and adult (beta) genes. Their deduced amino acid sequences are unlike any
previously reported fetal or adult globins; rather, comparison to other
mammalian globin genes indicates that they are embryonic in nature. The
sequence data indicate that these two genes have converted each other
during evolution. Pairwise comparison to the corresponding goat genes shows
greater similarity between paralogues than between more directly related
orthologues. This is in direct contrast to the situation between the cow
and goat fetal and adult genes. These observations suggest that the
frequency of DNA conversion or the fixation of conversion events may vary
in different locations of the cow beta-globin cluster.
相似文献
140.