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101.
The Salmonella mutagenicity test (Ames assay) is part of the routine screening battery applied to all new drugs at The Upjohn Company. The purpose of this paper is to report results for 29 compounds. These compounds are very diverse in chemical structure and represent classes of compounds selected because of known biological activity and other reasons. None of the compounds reported here produced an increase in revertant colonies in the Salmonella strains employed (TA98, TA100, TA1535, TA1537 and TA1538) and therefore the Salmonella mutagenicity results with these materials do not suggest potential for mutagenesis or carcinogenesis. 相似文献
102.
103.
The age- and cytomegalovirus (CMV)-seropositivity-related changes in subsets and differentiation of circulating T cells were investigated in end-stage renal disease (ESRD) patients (n = 139) and age-matched healthy individuals. The results show that CMV-seropositivity is associated with expansion of both CD4+ and CD8+ memory T cells which is already observed in young healthy individuals. In addition, CMV-seropositive healthy individuals have a more differentiated memory T cell profile. Only CMV-seropositive healthy individuals showed an age-dependent decrease in CD4+ naïve T cells. The age-related decrease in the number of CD8+ naïve T cells was CMV-independent. In contrast, all ESRD patients showed a profound naïve T-cell lymphopenia at every decade. CMV-seropositivity aggravated the contraction of CD4+ naïve T cells and increased the number of differentiated CD4+ and CD8+ memory T cells. In conclusion, CMV-seropositivity markedly alters the homeostasis of circulating T cells in healthy individuals and aggravates the T cell dysregulation observed in ESRD patients. 相似文献
104.
Gilles A. Spoden Ursula Rostek Stefan Lechner Maria Mitterberger Sybille Mazurek Werner Zwerschke 《Experimental cell research》2009,315(16):2765-2774
The glycolytic key regulator pyruvate kinase M2 (M2-PK or PKM2) can switch between a highly active tetrameric and an inactive dimeric form. The transition between the two conformations regulates the glycolytic flux in tumor cells. We developed specific M2-PK-binding peptide aptamers which inhibit M2-PK, but not the 96% homologous M1-PK isoenzyme. In this study we demonstrate that, at normal blood glucose concentrations, peptide aptamer-mediated inhibition of M2-PK induces a significant decrease of the population doubling (PDL rate) and cell proliferation rate as well as an increase in cell size, whereas under glucose restriction an increase in PDL and cell proliferation rates but a decrease in cell size was observed. Moreover, M2-PK inhibition rescues cells from glucose starvation-induced apoptotic cell death by increasing the metabolic activity. These findings suggest that M2-PK is a metabolic sensor which regulates cell proliferation, cell growth and apoptotic cell death in a glucose supply-dependent manner. 相似文献
105.
Christopher P Keller Richard R Barkosky Joshua E Seil Shanna A Mazurek Morgan L Grundstad 《Plant signaling & behavior》2008,3(9):633-640
Previous reports have suggested the primary mode of action of the allelochemical hydroquinone involves disruption of root cell membrane transport. Here we report the effects of hydroquinone on common bean (Phaseolus vulgaris) plants. Growth of leaves, roots and stems were all inhibited by 14 day exposure to 0.01 mM or 0.25 mM hydroquinone. Chlorophyll fluorescence (Fv/Fm) was inhibited by 0.25 mM hydroquinone. The membrane potential of P. vulgaris root cortex cells briefly hyperpolarized and subsequently slowly transiently depolarized upon abrupt exposure to a range of hydroquinone concentrations. Both the hyperpolarization and depolarization were concentration dependent but appeared saturable. Root cells exposed to 0.03 mM hydroquinone hyperpolarized 3.4 mV (+/− 0.6 s.e.) 3 minutes after the start of exposure then depolarized 36.7 mV (+/− 3.9) with no effect evident after 24 hours. Individual recordings showed a response to as little as 0.001 mM hydroquinone. Exposure of P. vulgaris root cells to arbutin, a nontoxic monoglucoside of hydroquinone, produced a similar but much smaller (approximately 25%) electrical response. Exposure of root cells of Antennaria microphylla, a known allelopathic source (donor plant) of hydroquinone, also produced a much smaller hyperpolarization and depolarization response. It is concluded that the electrical response to hydroquinone by P. vulgaris root cells and the changes in membrane transport they represent are not sufficiently large or long lasting enough to disrupt mineral and water uptake leading to plant injury. The possibility, however, that these events are related to initiation of signal transduction events leading to cell death is discussed.Key words: allelopathy, hydroquinone, membrane potential, depolarization, hyperpolarization, Phaseolus vulgaris, Antennaria microphylla 相似文献
106.
A characteristic feature of the sperm P1 protamines of eutherian mammals is
the constant presence of six to nine cysteine residues per molecule. During
spermiogenesis these residues become oxidized to form a three-dimensional
network of disulfide bridges between, and within, protamine molecules in
the sperm chromatin. This covalent cross linking strongly stabilizes
eutherian sperm nuclei. In contrast, protamines sequenced from teleost
fish, birds, monotremes, and marsupials all lack cysteine residues and
their sperm nuclei, without the stabilizing cross links, are easily
decondensed in vitro. We have now found that one genus of tiny, shrewlike
dasyurid marsupials, the Planigales, possess P1 protamines containing five
to six cysteine residues. These residues appear to have evolved since the
divergence of Planigales from other members of the family Dasyuridae, such
as the marsupial mouse, Sminthopsis crassicaudata. We believe this
constitutes a case of convergent evolution in a subfamily of dasyurid
marsupials toward the cysteine-rich eutherian form of sperm protamine P1.
相似文献
107.
108.
Mazurek N Sun YJ Liu KF Gilcrease MZ Schober W Nangia-Makker P Raz A Bresalier RS 《The Journal of biological chemistry》2007,282(29):21337-21348
Galectin-3 (GAL3), a beta-galactoside-binding lectin, confers chemoresistance to a wide variety of cancer cell types. It may exhibit anti- or pro-apoptotic activity depending on the nature of the stimulus. We report here that introducing phosphorylated galectin-3 (P-GAL3) into GAL3-null, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant human breast carcinoma cells promotes TRAIL-induced apoptotic cell death by stimulating the phosphorylation/inactivation of the pro-apoptotic molecule Bad resulting in the inhibition of mitochondrial depolarization and the release of cytochrome c. Exposure of the transfectant cells to TRAIL leads to the recruitment of the initiator capase-8 followed by activation of the effector caspase-9, independent of cytochrome c, and subsequently the processing of the executioner caspase-3. P-GAL3 and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) were coordinately expressed, with concomitant dephosphorylation of Akt in TRAIL-sensitive cells. In contrast, overexpression of phospho-mutant GAL3 (incapable of phosphorylation) failed to elicit similar responses. Depletion of PTEN using small interference RNAs reinstated Akt phosphorylation and conferred TRAIL resistance. In addition phosphatidylinositol 3-kinase inhibitors rendered the phospho-mutant GAL3-resistant cells sensitive to TRAIL. These findings suggest a pivotal role for P-GAL3 in promoting TRAIL sensitivity through activation of a nonclassic apoptotic pathway and identify P-GAL3 as a novel regulator of PTEN. 相似文献
109.
Unusual interferon gamma measurements with QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube tests
Introduction
Interferon gamma (IFN-γ) release assays, such as QuantiFERON®-TB Gold test (QFT-G) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect M. tuberculosis (Mtb) infection. Recognition of unusual IFN-γ measurements may help indicate inaccurate results.Methods
We examined QFT-G and QFT-GIT results from subjects who had two or more tests completed. We classified unusual IFN-γ measurements as: 1) High Nil Concentration (HNC) when IFN-γ concentration in plasma from unstimulated blood exceeded 0.7 IU/mL; 2) Low Mitogen Response (LMR) when Mitogen Response was <0.5 IU/mL; 3) Very Low Mitogen Response (VLMR) when Mitogen Response was ≤−0.5 IU/mL; and 4) Very Low Antigen Response (VLAR) when the response to a Mtb antigen was ≤−0.35 IU/mL and ≤−0.5 times the IFN-γ concentration in plasma from unstimulated blood.Results
Among 5,309 results from 1,728 subjects, HNC occurred in 234 (4.4%) tests for 162 subjects, LMR in 108 (2.0%) tests for 85 subjects, VLMR in 22 (0.4%) tests for 21 subjects, and VLAR in 41 (0.8%) tests for 39 subjects. QFT-GIT had fewer HNC, VLMR, and VLAR (p = 0.042, 0.004, and 0.067 respectively); QFT-G had fewer LMR (p = 0.005). Twenty-four (51.6%) of 47 subjects with positive results and HNC were negative or indeterminate by all other tests. Thirteen (61.9%) of 21 subjects with positive results and LMR were negative or indeterminate by all other tests.Conclusion
Unusual IFN-γ measurements including HNC, LMR, VLMR, and VLAR were encountered in small numbers, and in most instances were not seen on simultaneously or subsequently performed tests. To avoid erroneous diagnosis of Mtb infection, IGRAs with unusual IFN-γ measurements should be repeated with another blood sample and interpreted with caution if they recur. 相似文献110.