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111.
I Kogan-Sakin Y Tabach Y Buganim A Molchadsky H Solomon S Madar I Kamer P Stambolsky A Shelly N Goldfinger S Valsesia-Wittmann A Puisieux A Zundelevich E N Gal-Yam C Avivi I Barshack M Brait D Sidransky E Domany V Rotter 《Cell death and differentiation》2011,18(2):271-281
A mutation within one allele of the p53 tumor suppressor gene can inactivate the remaining wild-type allele in a dominant-negative manner and in some cases can exert an additional oncogenic activity, known as mutant p53 ‘gain of function'' (GOF). To study the role of p53 mutations in prostate cancer and to discriminate between the dominant-negative effect and the GOF activity of mutant p53, we measured, using microarrays, the expression profiles of three immortalized prostate epithelial cultures expressing wild-type, inactivated p53 or mutated p53. Analysis of these gene expression profiles showed that both inactivated p53 and p53R175H mutant expression resulted in the upregulation of cell cycle progression genes. A second group, which was upregulated exclusively by mutant p53R175H, was predominantly enriched in developmental genes. This group of genes included the Twist1, a regulator of metastasis and epithelial–mesenchymal transition (EMT). Twist1 levels were also elevated in metastatic prostate cancer-derived cell line DU145, in immortalized lung fibroblasts and in a subset of lung cancer samples, all in a mutant p53-dependent manner. p53R175H mutant bearing immortalized epithelial cells showed typical features of EMT, such as higher expression of mesenchymal markers, lower expression of epithelial markers and enhanced invasive properties in vitro. The mechanism by which p53R175H mutant induces Twist1 expression involves alleviation of the epigenetic repression. Our data suggest that Twist1 expression might be upregulated following p53 mutation in cancer cells. 相似文献
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Anti-interleukin 2 receptor antibody suppresses delayed-type hypersensitivity to foreign and syngeneic antigens 总被引:4,自引:0,他引:4
V E Kelley D Naor N Tarcic G N Gaulton T B Strom 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(7):2122-2124
Delayed-type hypersensitivity (DTH) requires stimulation of antigen-specific helper T cells (Th). Because de novo expression of the interleukin 2 receptor (IL 2R) is a necessary step in T cell activation, we tested the capacity of anti-mouse IL 2R monoclonal antibody (Mab) and anti-Th Mab (anti-L3T4) to block DTH. We examined the effect of these Mab on two distinct DTH systems, i.e., to foreign hapten (trinitrobenzenesulfonic acid) and to this hapten present on syngeneic blasts. Both anti-IL 2R and anti-L3T4 Mab suppress DTH. Therapy is as effective treating with one injection just before challenge with the hapten as giving six daily injections. These data indicate that DTH is dependent on a discrete subset of activated IL 2R-positive T cells, because anti-IL 2R therapy, which targets few cells, is as effective as anti-L3T4 Mab treatment, which targets the entire Th subset. 相似文献
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Stimulation of cultured pituitary cells from a gonadotrope lineage (alpha T3-1) by the gonadotropin-releasing hormone agonist analog [D-Trp6]GnRH (GnRH-A) resulted in a manifold increase in accumulation of phosphatidylethanol, a specific product of phospholipase D phosphatidyl transferase activity when ethanol is the phosphatidyl group acceptor. Levels of the natural lipid product of phospholipase D, phosphatidic acid, were increased 2-3-fold. Activation of phospholipase D by GnRH-A was dose- and time-dependent and was blocked by a GnRH receptor antagonist [D-pClPhe2,D-Trp3.6]GnRH. GnRH-A stimulated phospholipase D activity after a lag of 1-2 min. We conclude that in alpha T3-1 gonadotropes GnRH receptor occupancy results in delayed activation of phospholipase D which could participate in late phases of gonadotrope regulation by the neurohormone. 相似文献
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GABA signalling during development: new data and old questions 总被引:9,自引:0,他引:9
Patricia Varju Zoya Katarova Emilia Madarász Gábor Szabó 《Cell and tissue research》2001,305(2):239-246
In addition to being the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is thought to play a morphogenetic role in embryonic development. During the last decade, considerable progress has been made in elucidating the molecular mechanisms involved in GABA synthesis and biological action. The present review is an attempt to summarise recent results on the ontogeny of the different components of embryonic GABA signalling with an emphasis on the synthesis of GABA by different molecular forms of glutamic acid decarboxylase (GAD). 相似文献
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1. The biogenic amine histamine develops effects not only in mammalian cells and tissues but in ciliated unicellular Tetrahymena as well. In addition to binding and internalization of labelled histamine, low concentrations can stimulate the phagocytosis of cells in inorganic salt solution. 2. In inorganic solution Tetrahymena cells secrete acid hydrolases to the medium. High concentration of histamine (10 mM) decreases the secretion of three investigated acid hydrolases in a different manner. We think that in this process the primary determinant is the alkaline character of histamine. 3. The effect of histamine on phagocytosis differs from the effect on secretion since the low, physiological concentration of histamine stimulates phagocytosis, the higher concentrations inhibit it. In the background of these effects possibly the hormone character is dominant. It is supported by the fact that histamine antagonists influence the process differently. 相似文献