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Intratumoral interleukin-2 immunotherapy: Activation of tumor-infiltrating and splenic lymphocytes in vivo 总被引:5,自引:1,他引:4
Steven M. Dubinett Lisa Patrone Jeffery Tobias Alistair J. Cochran Duan-Ren Wen William H. McBride 《Cancer immunology, immunotherapy : CII》1993,36(3):156-162
Direct intratumoral injection of interleukin-2 (IL-2) was evaluated in a murine model. Balb/c mice received 5 × 104 Line 1 alveolar carcinoma cells (L1C2) by subcutaneous injection. On the third day following tumor implantation, mice received injections of IL-2 (5 × 103–5 × 104 units) or diluent twice daily, either by i. p. or intratumoral injection, 5 days/week for 3 weeks. Intratumoral injection of 5 × 104 units IL-2 significantly reduced tumor volume (P <0.05 versus control), increased median survival time (P = 0.0001), and resulted in a 23.5% cure rate (P = 0.008). There were no long-term survivors in the other treatment groups. Both tumor-infiltrating lymphocytes (TIL) and splenic lymphocytes isolated directly from IL-2-treated mice demonstrated enhanced cytolytic activity compared to diluent-treated controls. To determine whether non-T-cell-mediated antitumor responses were active in our model, intratumoral immunotherapy was evaluated in athymic Balb/cnu/nu mice. In order to decrease the recruitment of lymphocyte precursors, nude mice were splenectomized and received cyclophosphamide prior to tumor injection and IL-2 therapy. Intratumoral IL-2 immunotherapy also significantly decreased tumor volume in these immunodeficient mice (P <0.02), but did not lead to long-term survival. We conclude that both TIL and splenic lymphocytes are activated in vivo in response to intratumoral IL-2 immunotherapy, suggesting that intratumoral therapy with IL-2 activates both local and systemic antitumor responses.Supported by the Tobacco-Related Disease Research Program of the University of California, the Cancer Research Coordinating Committee, the Jonsson Cancer Center Foundation, and Veterans Administration Medical Research Funds 相似文献
34.
Rco-3, a Gene Involved in Glucose Transport and Conidiation in Neurospora Crassa 总被引:2,自引:0,他引:2 下载免费PDF全文
Macroconidiation in Neurospora crassa is influenced by a number of environmental cues, including the nutritional status of the growing organism. Conidia formation is normally observed when the fungus is exposed to air. However, carbon limitation can induce conidiation in mycelia submerged in an aerated liquid medium. A mutant was previously isolated that could conidiate in submerged culture without imposing nutrient limitation and the gene responsible for this phenotype (rco-3) has now been cloned. RCO3 exhibits sequence similarity to members of the sugar transporter gene superfamily, with greatest similarity to glucose transporters of yeast. Consistent with this structural similarity, we find that glucose transport activity is altered in the mutant. However, growth of the mutant in media containing alternate carbon sources does not suppress conidiation in submerged culture. The properties of the mutant suggest that RCO3 is required for expression of glucose transport activity, glucose regulation of gene expression, and general carbon repression of development. 相似文献
35.
Muriel Bost Mary Berkaw O. Wesley McBride Guy Chazot Philippe Arnaud 《Human genetics》1995,96(2):239-240
Using a probe isolated from a human liver cDNA library, polymorphisms were observed in the human ceruloplasmin gene with the enzymes PstI and MspI. The PstI polymorphism was frequent (allele frequencies, 0.46 and 0.54) whereas the polymorphisms found with MspI were rare. 相似文献
36.
D Przepiorka S B Baylin O W McBride J R Testa A de Bustros B D Nelkin 《Biochemical and biophysical research communications》1984,120(2):493-499
By molecular hybridization of human calcitonin cDNA probes to DNA from human-rodent hybrid cells containing identified human chromosomes, we have mapped the human calcitonin gene to the short arm of chromosome 11. This location has been confirmed by in situ hybridization, which further localized the calcitonin gene to region 11p13-15. The significance of this region regarding gene linkage and possible markers for inherited cancers is discussed. 相似文献
37.
M E McBride 《Applied microbiology》1984,48(2):338-341
A comparison has been made of the in-use bacterial load of two bar soaps with and without antibacterials and two liquid soaps in five different locations over a 1-week period. Of the 25 samples taken from each soap, 92 to 96% of samples from bar soaps were culture positive as compared to 8% of those from liquid soaps. Bacterial populations ranged from 0 to 3.8 log CFU per sample for bar soaps and from 0 to 2.0 log CFU per sample for liquid soaps. The mean bacterial populations per sample were 1.96 and 2.47 log CFU for the two bar soaps, and 0.08 and 0.12 log CFU for the two liquid soaps. The difference in bacterial population between bar soaps and liquid soaps was statistically significant (P = 0.005). Staphylococcus aureus was isolated on three occasions from bar soaps but not from liquid soaps. S. aureus was isolated twice from the exterior of the plastic dispensers of liquid soap but not from the soap itself. Gram-negative bacteria were cultured only from soaps containing antibacterials. Bacterial populations on bar soaps were not high compared with bacterial populations on hands, and the flora was continually changing without evidence of a carrier state. 相似文献
38.
Abstract— Crude synaptosomal (P2) preparations were obtained from the cerebella of rats in which the granule cell population had been selectively reduced by X-irradiation treatment and from the cerebella of control animals. In the P2 fraction from control cerebella, the level of glutamate was greater than any other of the 5 amino acids measured and was 2-fold higher than taurine, which was present at the next highest level. The content of taurine was slightly higher than that found for aspartate and was 3-fold greater than that observed for GABA. Alanine and glycine were present in the lowest amounts. The levels of glutamate and aspartate were significantly (P < 0.05) lower by 25 and 15%, respectively, in the P2 fraction isolated from the X-irradiated cerebella in comparison to control values. The content of taurine, GABA, glycine, and alanine were not changed by the X-irradiation treatment. The uptake of 1.0 μm -l -[3H]glutamate and l -[3H]aspartate was reduced approx 20% by X-irradiation treatment, whereas the uptake of 1.0 μm -[3H]GABA and [3H]taurine was unchanged. A more detailed kinetic analysis of l -[3H]glutamate uptake revealed there was a 20% decrease in the Vmax value with X-irradiation treatment and no change in the apparent Km value. In a second study, the uptake of l -[3H]glutamate, l -[3H]aspartate and [3H]GABA was measured using P2 fractions obtained from the cerebella of rats in which the population of granule, stellate and basket cells had been reduced by X-irradiation treatment. The uptake of 1.0μm -l -[3H]glutamate, l -[3H]aspartate and [3H]GABA was significantly (P < 0.05) reduced to 57, 68, and 59%, respectively, of control values. A more detailed kinetic analysis of [3H]GABA uptake revealed no significant change in the apparent Km and a 35% decrease in the Vmax value. The data are discussed in terms of glutamate being the excitatory neurotransmitter released from granule cells and GABA being the inhibitory neurotransmitter released from basket cells. 相似文献
39.
The effect of the x-irradiation-induced loss of cerebellar granule and stellate cells on the levels of glutamate, aspartate and GABA in regions of the rat cerebellum was determined. The level of glutamate was significantly lower in the neuron-depleted cerebellar cortex while GABA levels were higher than control values in the cerebellar cortex and white matter of the x-irradiated rats. Aspartate levels were not changed by x-irradiation in any cerebellar region. The data is discussed in terms of the proposed role of glutamate as the excitatory neurotransmitter released from granule cells. 相似文献
40.
The metabolic response to L-lysine of Escherichia coli ATCC 13002, a lysine-histidine double auxotroph, has been examined in a synthetic medium containing sucrose. In shaken cultures largest amounts of extracellular DAP were produced with an initial lysine concentration of 7·5 mg/1 and in static cultures of 2·5 mg/1. Considerably smaller amounts of DAP accumulated under stationary conditions. In cultures shaken for 20 and 43 h there was an overall decrease in the yields of DAP, expressed in terms of cell biomass and of sucrose consumed, as the initial concentration of lysine was increased from 0·75 mg/1 in steps up to 25 mg/1. The regulatory effect of lysine on DAP production was also observed when lysine was supplied to cultures at a constant rate employing diffusion capsules. 相似文献