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41.
Genetic polymorphims in promoter region of osteopontin gene may be a marker reflecting hepatitis activity in chronic hepatitis C patients 总被引:2,自引:0,他引:2
Mochida S Hashimoto M Matsui A Naito M Inao M Nagoshi S Nagano M Egashira T Mishiro S Fujiwara K 《Biochemical and biophysical research communications》2004,313(4):1079-1085
BACKGROUND AND AIMS: Osteopontin, an extracellular matrix protein with RGD motif, is shown to be a cytokine essential for Th1 immune response initiation. Genetic polymorphisms in the osteopontin gene (OPN) determine the magnitude of immunity against rickettsial infection in mice. Similar polymorphisms, if present also in human beings, might affect hepatitis activity in those infected with HCV. METHODS: Blood was collected from 176 patients with chronic hepatitis C. SNPs in the promoter region of OPN were analyzed in 20 patients by direct sequencing of DNA fragments amplified by PCR and in 156 patients by Invader assay. Ninety-five patients compatible to evaluation criteria were classified into three groups depending on maximal serum ALT levels during the observation periods at least for 2 years as follows; lower than 30IU/L (low-activity group), between 30 and 80IU/L with no hepatoprotective treatment (medium-activity group), and higher than 80IU/L irrespective of hepatoprotective treatment (high-activity group). RESULTS: There were 16, 19, and 60 patients in the low-, medium-, and high-activity groups, respectively. Four SNPs (nt -155, -443, -616, and -1748) were detected in the promoter region of OPN. Among them, the SNP at nt -443 (C or T) was a novel one and showed an association with hepatitis activity in our patients: T/T homozygosity was found in 2 (13%), 8 (42%), and 25 (44%), and C/T heterozygosity in 12 (75%), 8 (42%), and 23 (40%), in the low-, medium-, and high-activity groups, respectively. The other 3 SNPs already known showed linkage disequilibrium with D(') and r(2) greater than 0.937 to each other without correlation to disease activity. CONCLUSIONS. OPN promoter region SNP at nt -433 may be a useful marker reflecting hepatitis activity in chronic hepatitis C patients. 相似文献
42.
Hiroshi Shinmoto Yasunori Naganawa Michie Shimmoto Soheila J. Maleki 《Cytotechnology》2004,46(1):19-23
Two clones of mouse–human hybridomas, secreting human monoclonal antibodies to a peanut allergen Ara h1, were generated from human peripheral blood lymphocytes transformed with Epstein--Barr virus, followed by cell fusion with mouse myeloma cells. Epitope analysis with overlapping peptides synthesized on a multi-pin apparatus revealed antibody-binding sequences of Ara h1 protein. 相似文献
43.
Alison M. Michie Graham Rena Margaret M. Harnett Miles D. Houslay 《Cell biochemistry and biophysics》1998,28(2-3):161-185
We have previously shown that the major cAMP phosphodiesterase (PDE) isoforms present in murine thymocytes are the cGMP-stimulated
PDE activity (PDE-2) and the cAMP-specific PDE activity (PDE-4), and that these isoforms are differentially regulated following
ligation of the TCR (Michie, A. M., Lobban, M. D., Mueller, T., Harnett, M. M., and Houslay, M. D. [1996]Cell. Signalling
8, 97–110). We show here that the anti-CD3-stimulated elevation in PDE-4 activity in murine thymocytes is dependent on protein
tyrosine kinase and protein kinase C (PKC)-mediated signals as the TCR-coupled increase in PDE-4 activity can be abrogated
by both the tyrosine kinase inhibitor, genistein, and the PKC selective inhibitors chelerythrine and staurosporine. Moreover,
the PKC-activating phorobol ester, phorbol-12-myristate, 13-acetate (PMA) caused an increase in PDE-4 activity, similar to
that observed in cells challenged with anti-CD3 monoclonal antibodies and which was not additive with cochallenge using anti-CD3
antibodies. Both the PMA-and the anti-CD3 antibody-mediated increases in PDE-4 activity were blocked by treatment with either
cycloheximide or actinomycin D. Despite the upregulation of PDE-4 activity consequent to TCR ligation, intracellular cAMP
levels increased on challenge of thymocytes with anti-CD3 antibody, indicating that adenylate cyclase activity was also increased
by TCR ligation. It is suggested that the anti-CD3-mediated increase in PDE-4 activity was owing to a rapid PKC-dependent
induction of PDE-4 activity following crosslinking of the TCR complex. This identifies “crosstalk” occurring between the PKA
and PKC signaling pathways initiated by ligation of the antigen receptor in murine thymocytes. That both adenylate cyclase
and PDE-4 activities were increased may indicate the presence of compartmentalized cAMP responses present in these cells. 相似文献
44.
Disruption or absence of hepatocyte keratins 8 and 18 is associated with chronic hepatitis, marked hepatocyte fragility, and a significant predisposition to stress-induced liver injury. In contrast, pancreatic keratin disruption in transgenic mice that express keratin 18 Arg89 --> Cys (K18C) is not associated with an obvious pancreatic pathology. We compared the effects of keratin filament disruption on pancreatic acini or acinar cell viability, and on cholecystokinin (CCK)-stimulated secretion, in transgenic mice that overexpress wild-type keratin 18 and harbor normal extended keratin filaments (TG2) and K18C mice. We also compared the response of these mice to pancreatitis induced by a choline-deficient ethionine-supplemented diet or by caerulein. Despite extensive cytoplasmic keratin filament disruption, the apicolateral keratin filament bundles appear intact in the acinar pancreas of K18C mice, as determined ultrastructurally and by light microscopy. No significant pancreatitis-associated histologic, serologic, or F-actin/keratin apicolateral redistribution differences were noted between TG2 and K18C mice. Acinar cell viability and yield after collagenase digestion were lower in K18C than in TG2 mice, but the yields of intact acini and their (125)I-CCK uptake and responses to CCK-stimulated secretion were similar. Our results indicate that keratin filament reorganization is a normal physiologic response to pancreatic cell injury, but an intact keratin cytoplasmic filament network is not as essential in protection from cell injury as in the liver. These findings raise the possibility that the abundant apicolateral acinar keratin filaments, which are not as evident in hepatocytes, may play the cytoprotective role that is seen in liver and other tissues. Alternatively, identical keratins may function differently in different tissues. 相似文献
45.
Paul REL Lafond T Müller-Graf CDM Nithiuthai S Brey PT Koella JC 《BMC evolutionary biology》2004,4(1):1-13
Background
Theoretical studies suggest that direct and indirect selection have the potential to cause substantial evolutionary change in female mate choice. Similarly, sexual selection is considered a strong force in the evolution of male attractiveness and the exaggeration of secondary sexual traits. Few studies have, however, directly tested how female mate choice and male attractiveness respond to selection. Here we report the results of a selection experiment in which we selected directly on female mating preference for attractive males and, independently, on male attractiveness in the guppy, Poecilia reticulata. We measured the direct and correlated responses of female mate choice and male attractiveness to selection and the correlated responses of male ornamental traits, female fecundity and adult male and female survival.Results
Surprisingly, neither female mate choice nor male attractiveness responded significantly to direct or to indirect selection. Fecundity did differ significantly among lines in a way that suggests a possible sexually-antagonistic cost to male attractiveness.Conclusions
The opportunity for evolutionary change in female mate choice and male attractiveness may be much smaller than predicted by current theory, and may thus have important consequences for how we understand the evolution of female mate choice and male attractiveness. We discuss a number of factors that may have constrained the response of female choice and male attractiveness to selection, including low heritabilities, low levels of genetic (co)variation in the multivariate direction of selection, sexually-antagonistic constraint on sexual selection and the "environmental covariance hypothesis".46.
High-quality RNA from cells isolated by laser capture microdissection 总被引:11,自引:0,他引:11
Mikulowska-Mennis A Taylor TB Vishnu P Michie SA Raja R Horner N Kunitake ST 《BioTechniques》2002,33(1):176-179
Laser capture microdissection (LCM) provides a rapid and simple method for procuring homogeneous populations of cells. However, reproducible isolation of intact RNAfrom these cells can be problematic; the sample may deteriorate before or during sectioning, RNA may degrade during slide staining and LCM, and inadequate extraction and isolation methods may lead to poor recovery. Our report describes an optimized protocol for preparation of frozen sections for LCM using the HistoGene Frozen Section Staining Kit. This slide preparation method is combined with the PicoPure RNA Isolation Kitfor extraction and isolation of RNA from low numbers of microdissected cells. The procedure is easy to perform, rapid, and reproducible. Our results show that the RNA isolated from the LCM samples prepared according to our protocol is of high quality. The RNA maintains its integrity as shown by RT-PCR detection of genes of different abundance levels and by electrophoretic analysis of ribosomal RNA. RNA obtained by this method has also been used to synthesize probes for interrogating cDNA microarray analyses to study expression levels of thousands of genes from LCM samples. 相似文献
47.
48.
49.
Harry W. Rathbone Jeffery A. Davis Katharine A. Michie Sophia C. Goodchild Neil O. Robertson Paul M. G. Curmi 《Biophysical reviews》2018,10(5):1427-1441
The role of non-trivial quantum mechanical effects in biology has been the subject of intense scrutiny over the past decade. Much of the focus on potential “quantum biology” has been on energy transfer processes in photosynthetic light harvesting systems. Ultrafast laser spectroscopy of several light harvesting proteins has uncovered coherent oscillations dubbed “quantum beats” that persist for hundreds of femtoseconds and are putative signatures for quantum transport phenomena. This review describes the language and basic quantum mechanical phenomena that underpin quantum transport in open systems such as light harvesting and photosynthetic proteins, including the photosystem reaction centre. Coherent effects are discussed in detail, separating various meanings of the term, from delocalized excitations, or excitons, to entangled states and coherent transport. In particular, we focus on the time, energy and length scales of energy transport processes, as these are critical in understanding whether or not coherent processes are important. The role played by the protein in maintaining chromophore systems is analysed. Finally, the spectroscopic techniques that are used to probe energy transfer dynamics and that have uncovered the quantum beats are described with reference to coherent phenomena in light harvesting. 相似文献
50.
Alexis Llewellyn Craig Whittington Gavin Stewart Julian PT Higgins Nick Meader 《PloS one》2015,10(12)