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561.
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563.
Craig A. Grapperhaus Majda Kreso Gretchen A. Burkhardt Julianna V.F. Roddy Mark S. Mashuta 《Inorganica chimica acta》2005,358(1):123-130
Alkylation of bis(2-aminoethanethiolato)nickel(II) (1) with alkylating agents containing pendant donor groups has been investigated. Reaction with 2-bromoethylamine is strictly sulfur-centered yielding (2-[(2-aminoethyl)thio]ethaneamine)nickel(II)bromide, [(DAES)2Ni]Br2 (2), which was isolated as a lilac solid. Addition of chloroacetamide yields the sulfur- and nitrogen-alkylated product (2-[(2-aminoethyl)thio]acetamide)nickel(II)chloride, (AETA)NiCl2 (3a), as a green solid. Recrystallization from water/acetone yields 3a as single crystals along with single crystals of [(AETA)NiCl(OH2)]Cl (3b). The strictly S-alkylated product (2-[(2-amino-2-oxoethyl)thio]acetamide)nickel(II)iodide, [(AOTA)2Ni]I2 (4), is obtained upon reaction of 1 with iodoacetamide. A pathway is proposed consistent with the observed leaving group effect on the site of alkylation. The X-ray structures of 3a, 3b, and 4 are reported and the hydrogen-bonding network is described. 相似文献
564.
López-Hernández GY Sánchez-Padilla J Ortiz-Acevedo A Lizardi-Ortiz J Salas-Vincenty J Rojas LV Lasalde-Dominicci JA 《The Journal of biological chemistry》2004,279(36):38007-38015
Desensitization induced by chronic nicotine exposure has been hypothesized to trigger the up-regulation of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) in the central nervous system. We studied the effect of acute and chronic nicotine exposure on the desensitization and up-regulation of different alpha4beta2 subunit ratios (1alpha:4beta, 2alpha:3beta, and 4alpha:1beta) expressed in Xenopus oocytes. The presence of alpha4 subunit in the oocyte plasmatic membrane increased linearly with the amount of alpha4 mRNA injected. nAChR function and expression were assessed during acute and after chronic nicotine exposure using a two-electrode voltage clamp and whole-mount immunofluorescence assay along with confocal imaging for the detection of the alpha4 subunit. The 2alpha4:3beta2 subunit ratio displayed the highest ACh sensitivity. Nicotine dose-response curves for the 1alpha4:4beta2 and 2alpha4:3beta2 subunit ratios displayed a biphasic behavior at concentrations ranging from 0.1 to 300 microm. A biphasic curve for 4alpha4:1beta2 was obtained at nicotine concentrations higher than 300 microm. The 1alpha4:4beta2 subunit ratio exhibited the lowest ACh- and nicotine-induced macroscopic current, whereas 4alpha4:1beta2 presented the largest currents at all agonist concentrations tested. Desensitization by acute nicotine exposure was more evident as the ratio of beta2:alpha4 subunits increased. All three alpha4beta2 subunit ratios displayed a reduced state of activation after chronic nicotine exposure. Chronic nicotine-induced up-regulation was obvious only for the 2alpha4: 3beta2 subunit ratio. Our data suggest that the subunit ratio of alpha4beta2 determines the functional state of activation, desensitization, and up-regulation of this neuronal nAChR. We propose that independent structural sites regulate alpha4beta2 receptor activation and desensitization. 相似文献
565.
Epidermal growth factor receptor transactivation mediates tumor necrosis factor-induced hepatocyte replication 总被引:7,自引:0,他引:7
Argast GM Campbell JS Brooling JT Fausto N 《The Journal of biological chemistry》2004,279(33):34530-34536
Tumor necrosis factor (TNF) has multiple biological effects such as participating in inflammation, apoptosis, and cell proliferation, but the mechanisms of its effects on epithelial cell proliferation have not been examined in detail. At the early stages of liver regeneration, TNF functions as a priming agent for hepatocyte replication and increases the sensitivity of hepatocytes to growth factors such as transforming growth factor alpha (TGFalpha); however, the mechanisms by which TNF interacts with growth factors and enhances hepatocyte replication are not known. Using the AML-12 hepatocyte cell line, we show that TNF stimulates proliferation of these cells through transactivation of the epidermal growth factor receptor (EGFR). The transactivation mechanism involves the release of TGFalpha into the medium through activation of the metalloproteinase TNFalpha-converting enzyme (also known as ADAM 17). Binding of the ligand to EGFR initiates a mitogenic cascade through extracellular signal-regulated kinases 1 and 2 and the partial involvement of protein kinase B. TNF-induced release of TGFalpha and activation of EGFR signaling were inhibited by TNFalpha protease inhibitor-1, an agent that interferes with TNFalpha-converting enzyme activity. We suggest that TNF-induced transactivation of EGFR may provide an early signal for the entry of hepatocytes into the cell cycle and may integrate proliferative and survival pathways at the start of liver regeneration. 相似文献
566.
Baker SC Bauer SR Beyer RP Brenton JD Bromley B Burrill J Causton H Conley MP Elespuru R Fero M Foy C Fuscoe J Gao X Gerhold DL Gilles P Goodsaid F Guo X Hackett J Hockett RD Ikonomi P Irizarry RA Kawasaki ES Kaysser-Kranich T Kerr K Kiser G Koch WH Lee KY Liu C Liu ZL Lucas A Manohar CF Miyada G Modrusan Z Parkes H Puri RK Reid L Ryder TB Salit M Samaha RR Scherf U Sendera TJ Setterquist RA Shi L Shippy R Soriano JV Wagar EA Warrington JA Williams M Wilmer F Wilson M Wolber PK Wu X 《Nature methods》2005,2(10):731-734
Standard controls and best practice guidelines advance acceptance of data from research, preclinical and clinical laboratories by providing a means for evaluating data quality. The External RNA Controls Consortium (ERCC) is developing commonly agreed-upon and tested controls for use in expression assays, a true industry-wide standard control. 相似文献
567.
Hollamby S Afema-Azikuru J Sikarskie JG Kaneene JB Bowerman WW Fitzgerald SD Cameron K Gandolf AR Hui GN Dranzoa C Rumbeiha WK 《Journal of wildlife diseases》2004,40(3):501-514
The purpose of this research was to evaluate persistent organic pollutant (POP) and mercury concentrations in tissues of African fish eagles (Haliaeetus vocifer) and Nile tilapia (Oreochromis niloticus) from Lake Victoria near Entebbe and Lake Mburo, Uganda. Marabou stork (Leptoptilos crumeniferus) nestlings from urban Kampala (40 km from Entebbe) also were sampled for POPs and mercury. Total mercury was measured in the breast feathers of eight nestling and 10 adult African fish eagles from Lake Mburo, 10 nestling and five adult African fish eagles from Lake Victoria near Entebbe, and 20 nestling marabou storks from Kampala from June 2002 through January 2003. Mercury concentrations in all samples were below levels associated with adverse effects in similar species. Mercury concentrations were significantly higher in eagle adults and nestlings from Entebbe than in adults and nestlings from Lake Mburo (P< or =0.05). No significant differences (P> or =0.05) were found in mercury concentrations between sexes or between the entire fish eagle population sampled at Entebbe and marabou stork nestlings sampled at nearby Kampala. Plasma samples from the same birds were analyzed for 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane, aldrin, hexachlorocyclohexane (alpha-HCH), dieldrin, endrin, heptachlor and their metabolites, as well as total polychlorinated biphenyls (PCBs). Nile tilapia whole-body cross sections collected from Lake Mburo (n=3) and Lake Victoria near Entebbe (n=8) also were analyzed for these POPs and mercury. No samples contained POPs or PCBs at the limits of detection except for 4,4'-1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene in five adult eagle plasma samples (0.0026+/-0.0015 ppm wet weight) and five Nile tilapia samples (0.002+/-0.001 ppm wet weight) from Entebbe. 相似文献
568.
VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis 下载免费PDF全文
Dong J Grunstein J Tejada M Peale F Frantz G Liang WC Bai W Yu L Kowalski J Liang X Fuh G Gerber HP Ferrara N 《The EMBO journal》2004,23(14):2800-2810
We generated VEGF-null fibrosarcomas from VEGF-loxP mouse embryonic fibroblasts to investigate the mechanisms of tumor escape after VEGF inactivation. These cells were found to be tumorigenic and angiogenic in vivo in spite of the absence of tumor-derived VEGF. However, VEGF derived from host stroma was readily detected in the tumor mass and treatment with a newly developed anti-VEGF monoclonal antibody substantially inhibited tumor growth. The functional significance of stroma-derived VEGF indicates that the recruitment of stromal cells is critical for the angiogenic and tumorigenic properties of these cells. Here we identified PDGF AA as the major stromal fibroblast chemotactic factor produced by tumor cells, and demonstrated that disrupting the paracrine PDGFR alpha signaling between tumor cells and stromal fibroblasts by soluble PDGFR alpha-IgG significantly reduced tumor growth. Thus, PDGFR alpha signaling is required for the recruitment of VEGF-producing stromal fibroblasts for tumor angiogenesis and growth. Our findings highlight a novel aspect of PDGFR alpha signaling in tumorigenesis. 相似文献
569.
Protein serine/threonine kinase CK2 (formerly casein kinase 2) is a ubiquitous protein kinase that plays key roles in cell growth, proliferation, and survival. We have shown previously that its molecular down-regulation induces apoptosis in cancer cells in culture. Here, we have employed a xenograft model of prostate cancer to extend these studies to determine whether antisense CK2alpha evokes a similar response in vivo. A single dose of antisense CK2alpha oligodeoxynucleotide given directly into the PC3-LN4 xenograft tumor in nude mouse induced a dose- and time-dependent tumor cell death in vivo. The tumor was completely resolved at the higher tested dose of the antisense. Cell death was due to apoptosis and correlated with a potent down-regulation of the CK2alpha message and loss of CK2 from the nuclear matrix in the xenograft tissue as well as in cancer cells in culture. These observations accorded with several of the earlier studies indicating that loss of CK2 from the nuclear matrix is associated with induction of apoptosis. Comparison of the effects of antisense CK2alpha oligodeoxynucleotide on cancer versus normal or noncancer cells showed that the concentration of antisense CK2alpha that elicited extensive apoptosis in tumor cells in culture or xenograft tumors in vivo had a relatively small or minimal effect on noncancer cells in culture or on normal prostate gland subjected to orthotopic injection of antisense oligodeoxynucleotide in vivo. The basis for the difference in sensitivity of cancer versus noncancer cells to antisense CK2alpha is unknown at this time; however, this differential response under similar conditions of treatment may be significant in considering the potential feasibility of targeting the CK2 signal for induction of apoptosis in cancer cells in vivo. Although much further work will be needed to establish the feasibility of targeting CK2 for cancer therapy, to our knowledge, this is the first report to provide important new evidence as an initial "proof of principle" for the potential application of antisense CK2alpha in cancer therapy, paving the way for future detailed studies of approaches to targeting CK2 in vivo to induce cancer cell death. 相似文献
570.
Lineage-specific gene duplication and loss in human and great ape evolution 总被引:7,自引:2,他引:5 下载免费PDF全文
Fortna A Kim Y MacLaren E Marshall K Hahn G Meltesen L Brenton M Hink R Burgers S Hernandez-Boussard T Karimpour-Fard A Glueck D McGavran L Berry R Pollack J Sikela JM 《PLoS biology》2004,2(7):e207
Given that gene duplication is a major driving force of evolutionary change and the key mechanism underlying the emergence of new genes and biological processes, this study sought to use a novel genome-wide approach to identify genes that have undergone lineage-specific duplications or contractions among several hominoid lineages. Interspecies cDNA array-based comparative genomic hybridization was used to individually compare copy number variation for 39,711 cDNAs, representing 29,619 human genes, across five hominoid species, including human. We identified 1,005 genes, either as isolated genes or in clusters positionally biased toward rearrangement-prone genomic regions, that produced relative hybridization signals unique to one or more of the hominoid lineages. Measured as a function of the evolutionary age of each lineage, genes showing copy number expansions were most pronounced in human (134) and include a number of genes thought to be involved in the structure and function of the brain. This work represents, to our knowledge, the first genome-wide gene-based survey of gene duplication across hominoid species. The genes identified here likely represent a significant majority of the major gene copy number changes that have occurred over the past 15 million years of human and great ape evolution and are likely to underlie some of the key phenotypic characteristics that distinguish these species. 相似文献