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121.
Podrabsky JE Javillonar C Hand SC Crawford DL 《American journal of physiology. Regulatory, integrative and comparative physiology》2000,279(6):R2344-R2348
A previous phylogenetic analysis among 15 taxa of the teleost fish Fundulus suggested that there should be thermal-adaptive differences in heart metabolism among populations. To test this hypothesis, the rate of oxygen consumption and the activities of all 11 glycolytic enzymes were measured in isolated heart ventricle from two populations of Fundulus heteroclitus. Heart ventricular metabolism is greater in a northern population versus a southern population of these fish. Analysis of the amount of glycolytic enzymes indicates that 87% of the variation in cardiac metabolism within and between populations is explained by the variation in three enzymes (pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and lactate dehydrogenase). These enzymes are the same three enzymes that were predicted to be important based on previously determined phylogenetic patterns of expression. Our data indicate that near-equilibrium enzymes, as well as classically defined rate-limiting enzymes, can also influence metabolism. 相似文献
122.
The use of a rapid ELISPOT assay to analyze peptide-specific immune responses in carcinoma patients to peptide vs. recombinant poxvirus vaccines 总被引:5,自引:0,他引:5
Arlen P Tsang KY Marshall JL Chen A Steinberg SM Poole D Hand PH Schlom J Hamilton JM 《Cancer immunology, immunotherapy : CII》2000,49(10):517-529
An enzyme-linked immunosorbent spot (ELISPOT) assay for interferon γ production has been used to analyze specific T cell
responses to a Flu 9-mer peptide, and a 9-mer peptide of carcinoembryonic antigen (CEA). Assays were performed on peripheral
blood mononuclear cells (PBMC) of HLA-A2-positive patients with CEA-expressing carcinomas, both before and after vaccination
with CEA-based vaccines, and from HLA-A2-positive healthy blood donors. The ELISPOT assay utilized aliquots of frozen PBMC,
and assays were performed after 24 h in culture with peptide to rule out any artifacts due to long-term in vitro stimulation
cycles. An internal standard was used for each assay to define reproducibility of the assay, and all samples from a given
patient (pre- and post-vaccination, with both the Flu and CEA peptides) were analyzed simultaneously. The results indicated
a trend towards healthy blood donors having higher levels of Flu-specific T cell precursors than do colon carcinoma patients,
but these results were not statistically significant (P = 0.06). On the other hand, slightly higher CEA-specific T cell responses were observed in cancer patients with CEA-expressing
carcinomas than in healthy blood donors. PBMC from two CEA-based vaccine clinical trials were analyzed for T cell responses
to the same CEA peptide and to the Flu control peptide. The first trial consisted of three monthly vaccinations of CEA peptide
(designated PPP) in adjuvant. The second trial consisted of cohorts receiving three monthly vaccinations of avipox-CEA recombinant
(designated AAA) or cohorts receiving a primary vaccination with recombinant vaccinia-CEA followed by two monthly vaccinations
with avipox-CEA (designated VAA). Few, if any, CEA-specific T cell responses were seen in the PPP vaccinations, while the
majority of patients receiving the poxvirus CEA recombinants demonstrated increases in CEA-specific T cell responses and no
increases in Flu-specific responses. CEA-specific IgG responses were also demonstrated in patients following recombinant CEA
poxvirus vaccinations. Statistical analyses of the T cell responses to the same CEA peptide demonstrated a P value of 0.028 for the recombinant poxvirus vaccines, as compared with the peptide vaccine. There were no differences seen
(P = 0.37) in Flu-specific responses after these two types of CEA vaccination. These results thus provide the first evidence
that poxvirus recombinant-based vaccines are more potent in the initiation of tumor-antigen-specific T cell responses than
vaccines employing peptide in adjuvant, when assays are conducted in an identical manner, and in defining responses to the
same peptide. These results also demonstrate for the first time that an ELISPOT assay, performed over a 24-h period and without
in vitro sensitization, can be successfully used to monitor immune responses to a tumor-associated antigen in cancer patients.
Received: 12 June 2000 / Accepted: 13 July 2000 相似文献
123.
Rates of protein synthesis are substantially depressed in diapause II embryos of Austrofundulus limnaeus. Inhibition of oxygen consumption and heat dissipation with cycloheximide indicates that 36% of the adenosine triphosphate (ATP) turnover in prediapausing embryos (8 d postfertilization [dpf]) is caused by protein synthesis; the contribution of protein synthesis to ATP turnover in diapause II embryos is negligible. In agreement with the metabolic data, incorporation of amino acids (radiolabeled via (14)CO(2)) into perchloric acid-precipitable protein decreases by over 93% in diapause II embryos compared with embryos at 8 dpf. This result represents a 36% reduction in energy demand because of depression of protein synthesis during diapause. Adjusting for changes in the specific radioactivity of the free amino acid pool at the whole-embryo level yields rates of protein synthesis that are artifactually high and not supportable by the observed rates of oxygen consumption and heat dissipation during diapause. This result indicates a regionalized distribution of labeled amino acids likely dictated by a pattern of anterior to posterior cell cycle arrest. AMP/ATP ratios are strongly correlated with the decrease in rates of protein synthesis, which suggests a role for adenosine monophosphate (AMP) in the control of anabolic processes. The major depression of protein synthesis during diapause II affords a considerable reduction in energy demand and extends the duration of dormancy attainable in these embryos. 相似文献
124.
Hoback WW Podrabsky JE Higley LG Stanley DW Hand SC 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2000,170(4):307-314
In this study, we compared survivorship, heat dissipation and biochemical features of anaerobiosis of two tiger beetle species
(Coleoptera: Cicindelidae) exposed to anoxia. One species commonly experiences environmental immersion from rainfall and snowmelt
(Cicindela togata), and the habitat of the other (Amblycheila cylindriformis) is not prone to flooding. The ancestral genus, A. cylindriformis, survives anoxia for only 2 days at 25 °C. In response to anoxia, these larvae immediately lose locomotory abilities, tissue
concentrations of ATP fall precipitously within 12 h, and significant amounts of lactate are quickly produced. In contrast,
C. togata larvae tolerate anoxia for 5 days. Heat dissipation is downregulated to a greater degree than that seen in A. cylindriformis (3.4% versus 14% of standard normoxic rate, respectively), the ability for locomotion is maintained and normoxic levels of
ATP are defended for at least 24 h. Lactate is not accumulated until well into anoxic bout, and significant amounts of alanine
are also produced. This study provides evidence that tiger beetles differ in physiological responses to anoxia, and that these
differences are correlated with flooding risk and with species distribution.
Accepted: 1 March 2000 相似文献
125.
Cyclo-oxygenases (COXs) catalyze the first committed step in the synthesis of the prostaglandins PGE(2), PGD(2), PGF(2alpha), PGI(2) and thomboxane A(2). Expression and enzymatic activity of COX-2, the inducible isoform of COX, are observed in several neurological diseases and result in significant neuronal injury. The neurotoxic effect of COX-2 is believed to occur through downstream effects of its prostaglandin products. In this study, we examined the function of PGD(2) and its two receptors DP1 and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) (DP2) in neuronal survival. PGD(2) is the most abundant prostaglandin in brain and regulates sleep, temperature and nociception. It signals through two distinct G protein-coupled receptors, DP1 and DP2, that have opposing effects on cyclic AMP (cAMP) production. Physiological concentrations of PGD(2) potently and unexpectedly rescued neurons in paradigms of glutamate toxicity in cultured hippocampal neurons and organotypic slices. This effect was mimicked by the DP1-selective agonist BW245C but not by the PGD(2) metabolite 15d-PGJ(2), suggesting that neuroprotection was mediated by the DP1 receptor. Conversely, activation of the DP2 receptor promoted neuronal loss. The protein kinase A inhibitors H89 and KT5720 reversed the protective effect of PGD(2), indicating that PGD(2)-mediated neuroprotection was dependent on cAMP signaling. These studies indicate that activation of the PGD(2) DP1 receptor protects against excitotoxic injury in a cAMP-dependent manner, consistent with recent studies of PGE(2) receptors that also suggest a neuroprotective effect of prostaglandin receptors. Taken together, these data support an emerging and paradoxical neuroprotective role of prostaglandins in the CNS. 相似文献
126.
Intracellular naturally occurring aromatic thiols such as ergothioneine and the ovothiols have been shown to play a variety of roles in cellular function. A detailed ab initio electronic structure analysis of these thiols is reported evaluating the thermodynamics of the reactions of these intracellular thiols with alkyl thiols, HO*, H2O2, ascorbate and their disulfides. 相似文献
127.
Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation 下载免费PDF全文
The organization of the endoplasmic reticulum (ER) in the cortex of Xenopus oocytes was investigated during maturation and activation using a green fluorescent protein chimera, immunofluorescence, and electron microscopy. Dense clusters of ER developed on the vegetal side (the side opposite the meiotic spindle) during maturation. Small clusters appeared transiently at the time of nuclear envelope breakdown, disappeared at the time of first polar body formation, and then reappeared as larger clusters in mature eggs. The appearance of the large ER clusters was correlated with an increase in releasability of Ca(2+) by IP(3). The clusters dispersed during the Ca(2+) wave at activation. Possible relationships of ER structure and Ca(2+) regulation are discussed. 相似文献
128.
In mammalian species, cyclic AMP receptor proteins (cARP) are the regulatory (R) subunits of cyclic AMP-dependent protein kinase (PKA), the cellular effector of cyclic AMP-mediated signal transduction. An isoform of the PKA type II R subunit (RII), cARP, is a polyfunctional protein, present in most tissues and cells. It is expressed in salivary and other glands of rodents, and secreted into the saliva of rats and Man. The aim of the present study was to determine the expression of cARP in human salivary glands using immunoelectron microscopy. Thin sections of normal salivary glands embedded in LR Gold resin were labeled with anti-cARP primary antibody, then with gold-conjugated secondary antibody. Labeling was present in the secretory granules and cytoplasm of parotid, submandibular (SMG) and sublingual gland serous cells. Quantitative analysis showed considerable variability in granule labeling from sample to sample, indicating shifts in expression and cellular location of cARP. Unlike rodent salivary glands, the granules of intercalated and striated duct cells also were labeled. The cytoplasm and granules of mucous cells of the SMG and sublingual glands were unlabeled, while the Golgi complex and filamentous bodies in these cells showed moderate reactivity. Mitochondria and nuclei of both serous and mucous cells were unlabeled. Labeling also was present in the connective tissue adjacent to the epithelial cells. The results indicate that serous cells of the parotid and SMG are the major source of salivary cARP. They also reveal significant species differences in the glandular distribution of RII. RII binds to cytoskeletal and nuclear proteins, and may function to regulate extracellular cyclic AMP levels. Thus, the tissue and cellular distribution of RII may serve as an index of regulation of gene expression and cell differentiation. 相似文献
129.
When replicating DNA is labeled sequentially with radioactive and density tracers and analyzed by equilibrium centrifugation, the fraction banding at heavier than normal density is inversely proportional to the rate of replication fork movement if there is a sharp transition from one tracer to the other on the newly synthesized chains (Painter and Schaefer, '69). Primate CV-1 DNA labeled for 5 to 30 minutes with 3H-dThd and then for three hours with BrdUrd in the presence of FdUrd bands in a bimodal distribution in alkaline CsCl, rather than in a continuous distribution with a skew toward heavier density seen when FdUrd is omitted and centrifugation is in neutral CsCl. The heavy density peak represents interspersion of both tracers in the DNA and is caused by slow transition from dThd to BrdUrd incorporation when the tracers are switched in the labeling medium. This may result from preferential uptake and incorporation of dThd over BrdUrd. Because of the interspersion, calculation of the rate of replication fork movement is inaccurate. Reversal of the labeling sequence with administration of the long density pulse before the radioactive pulse reduces the problem of interspersion. Using this sequence of labeling, estimates of the rate of fork movement of 0.36-0.38 micrometer/min are obtained when the 3H pulse time is long enough to allow accurate measurement of the fraction of heavy DNA. Analysis by fiber autoradiography yields a rate of 0.56 micrometer/min in the same cell line. If appropriate precautions are taken to minimize mixing of the two tracers in the precursor pool and to ensure that the fraction of heavy DNA is measured accurately, the hydrodynamic technique provides an objective method of measuring rate of fork movement that gives values only slightly lower than those obtained by autoradiography. 相似文献
130.
Isolation of a thymus hormone, LSH 总被引:2,自引:0,他引:2