全文获取类型
收费全文 | 17532篇 |
免费 | 1310篇 |
出版年
2023年 | 90篇 |
2022年 | 105篇 |
2021年 | 445篇 |
2020年 | 247篇 |
2019年 | 356篇 |
2018年 | 435篇 |
2017年 | 414篇 |
2016年 | 591篇 |
2015年 | 896篇 |
2014年 | 932篇 |
2013年 | 1219篇 |
2012年 | 1403篇 |
2011年 | 1315篇 |
2010年 | 855篇 |
2009年 | 762篇 |
2008年 | 966篇 |
2007年 | 994篇 |
2006年 | 931篇 |
2005年 | 829篇 |
2004年 | 770篇 |
2003年 | 689篇 |
2002年 | 678篇 |
2001年 | 242篇 |
2000年 | 210篇 |
1999年 | 211篇 |
1998年 | 195篇 |
1997年 | 134篇 |
1996年 | 115篇 |
1995年 | 108篇 |
1994年 | 110篇 |
1993年 | 94篇 |
1992年 | 144篇 |
1991年 | 111篇 |
1990年 | 112篇 |
1989年 | 94篇 |
1988年 | 78篇 |
1987年 | 75篇 |
1986年 | 70篇 |
1985年 | 70篇 |
1984年 | 81篇 |
1983年 | 74篇 |
1982年 | 48篇 |
1981年 | 52篇 |
1980年 | 32篇 |
1979年 | 53篇 |
1978年 | 30篇 |
1977年 | 30篇 |
1975年 | 42篇 |
1973年 | 34篇 |
1970年 | 28篇 |
排序方式: 共有10000条查询结果,搜索用时 225 毫秒
71.
Solubilization of the active vasoactive intestinal peptide receptor from human colonic adenocarcinoma cells 总被引:1,自引:0,他引:1
A el Battari J M Martin J Luis O Pouzol J Secchi J Marvaldi J Pichon 《The Journal of biological chemistry》1988,263(33):17685-17689
The non-ionic detergent n-octyl-beta-D-glucopyranoside was used to solubilize the VIP (vasoactive intestinal peptide) receptor from human colonic adenocarcinoma cell line HT29-D4. The binding of monoiodinated 125I-VIP to the solubilized receptor was specific, time-dependent, and reversible. Scatchard analysis of data obtained from competitive displacement of monoiodinated 125I-VIP by native VIP suggested the presence of two classes of VIP binding sites with Kd values of 0.32 and 46.7 nM. The binding capacities of these two classes were 1.7 x 10(10) and 30.2 x 10(10) sites/mg of proteins, respectively. The solubilized receptor retained the specificity of the human VIP receptor towards the peptides of the VIP/secretin/glucagon family. The order of potency in inhibiting monoiodinated 125I-VIP binding was VIP (IC50 = 1.0 x 10(-9) M) much greater than peptide histidine methionine amide (IC50 = 10(-7) M) greater than growth hormone-releasing factor (IC50 = 3 x 10(-7) M) greater than secretin (IC50 greater than 10(-6) M); glucagon had no effect on VIP binding. The reducing agent dithiothreitol inhibited in a dose-dependent manner the binding of 125I-VIP. Covalent cross-linking experiments between the solubilized receptor and 125I-VIP showed that after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography two major and one minor polypeptides of Mr 67,000, 72,000, and 83,000 were specifically labeled. When analyzed by gel filtration, the n-octyl-beta-D-glucopyranoside-solubilized 125I-VIP-receptor complex was resolved into two major peaks with molecular mass in the range of 60-70 and 270-300 kDa. Thus, the soluble form of the VIP receptor was probably a multimeric complex in which disulfide bonds may play an important role to hold the receptor in an active configuration. 相似文献
72.
The O2- -forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function 总被引:37,自引:0,他引:37
F Rossi 《Biochimica et biophysica acta》1986,853(1):65-89
73.
74.
Host-Symbiont Specificity Expressed during Early Adsorption of Rhizobium meliloti to the Root Surface of Alfalfa 总被引:7,自引:1,他引:6 下载免费PDF全文
Early (4 h) adsorption of Rhizobium meliloti L5-30 in low numbers to alfalfa roots in mineral solution was examined for competition with other bacterial strains. All tested competitor strains decreased the adsorption of L5-30 by extents which depended on the strain and its concentration. The decrease of adsorption by R. meliloti competitors (all of them infective in alfalfa) was nearly complete at saturation (97 to 99% decrease). All other heterologous rhizobia and Agrobacterium tumefaciens at saturating concentrations (106 to 107 per ml) decreased adsorption of L5-30 only partially, less than 60%. The differential effects of homologous and heterologous competitors indicate that initial adsorption of R. meliloti to the root surface of its host occurs in symbiont-specific as well as nonspecific modes and suggest the existence of binding sites on roots which are highly selective for the specific microsymbiont in the presence of other heterologous bacteria even in very unfavorable (less than 10−4) symbiont-competitor concentration ratios. 相似文献
75.
Isolation and Characterization of an Fe(III)-Chelating Compound Produced by Pseudomonas syringae 总被引:2,自引:2,他引:0 下载免费PDF全文
Luis Torres Jos E. Prez-Ortín Vicente Tordera Jos P. Beltrn 《Applied microbiology》1986,52(1):157-160
The phytopathogenic bacterium Pseudomonas syringae produces a fluorescent pigment when it is grown in iron-deficient media. This pigment forms a very stable Fe(III) complex that was purified in this form by using a novel procedure based on ultrafiltration and column chromatography. The Fe(III) complex has a molecular weight of 1,100 and contains 1 mol of Fe(III). The pigment is composed of an amino acid moiety with three threonines, three serines, one lysine, δ-N-hydroxyornithine, and a quinoline-type fluorescent chromophore. These features and its stability constant (in the range of 1032) suggest that the fluorescent pigment of P. syringae is related to the siderophores produced by another Pseudomonas species. 相似文献
76.
Quinone toxicity in hepatocytes without oxidative stress 总被引:6,自引:0,他引:6
The toxicity of quinones is believed to be mediated via redox cycling involving formation of semiquinone radicals which autoxidize to form active oxygen species. However, when the cytotoxicity of benzoquinones was compared using freshly isolated rat hepatocytes, benzoquinones which did not mediate oxidative stress were highly toxic. Thus, the benzoquinone analogs in decreasing order of cytotoxicity were 2-CH3-, 2-Br-, unsubstituted, 2,6-(CH3)2-, 2,5-(CH3)2-, and 2,3,5-(CH3)3-benzoquinone. Cellular thiols were rapidly depleted and glutathione (GSH) was converted to a quinone conjugate without oxidation to glutathione disulfide. No increase in cyanide-resistant respiration was observed and benzoquinone-induced cytotoxicity was not enhanced by inactivation of catalase or glutathione reductase. In contrast, duroquinone [2,3,5,6-(CH3)4-benzoquinone], which stimulated cyanide-resistant respiration and GSH oxidation, was only cytotoxic when catalase or glutathione reductase was inactivated. These results suggest that alkylation and/or oxidative stress may be important mechanisms in the cytotoxicity of benzoquinone derivatives. 相似文献
77.
G Berton L Zeni M A Cassatella F Rossi 《Biochemical and biophysical research communications》1986,138(3):1276-1282
The oxidative metabolism of human neutrophils has been studied after incubation of the cells with recombinant interferon-y. Neutrophils incubated for 2-4 hours with 2-50 U/ml recombinant interferon-y undergo a higher respiratory burst measured both as Oz consumption and Oz- production when stimulated with formyl-methionyl-leucyl-phenylalanine, Concanavalin A or phorbol myristate acetate. The potentiating effect of interferon-y requires more than one hour of incubation, is optimal at 20-50 U/ml and depends on the presence of serum in the incubation medium. The interferon effect depends on new protein synthesis. Cycloheximide at doses which do not alter the respiratory response of normal cells completely prevents the potentiating effect of interferon. 相似文献
78.
As earlier data suggested the importance of lipoxygenase activation for expression of human NK cell cytotoxicity, four different lipoxygenase inhibitors were tested for suppression of natural killer (NK) cell lysis. All inhibitors were found active at nontoxic concentrations with 50% inhibition at approximately 15 microM for nordihydroguaiaretic acid (NDGA). NK cell lysis could be reconstituted to NDGA-suppressed cells with leukotriene B4 (LTB4), the all-trans isomers 6-trans-LTB4 and 12-epi-6-trans-LTB4, and 20-COOH-LTB4. LTB4 reconstitution was best in the concentration range 1-100 pM and near control levels at both higher and lower concentrations. Herpesvirus Ateles-transformed killer T cells could also be inhibited by NDGA. These data indicate that lipoxygenase activity is required for human NK cell lysis and that several different LTB4-related products can restore NK activity in inhibited cells; they also suggest that the lipoxygenase pathway is present in the killer cell population. 相似文献
79.
V Della Bianca M Grzeskowiak P De Togni M Cassatella F Rossi 《Biochimica et biophysica acta》1985,845(2):223-236
Verapamil inhibits in human neutrophils the respiratory burst, the secretion and the change of transmembrane potential induced by formylmethionylleucylphenylalanine, a Ca2+-dependent stimulus, and by phorbol myristate acetate, a Ca2+-independent stimulus. Besides the blocking of Ca2+ channels, many mechanisms are responsible for the inhibition of neutrophil responses. In fact, verapamil (i) increases the intracellular cAMP concentration, potentiates the cAMP response induced by the chemotactic peptide and induces the appearance of a cAMP response also when the stimulant is phorbol myristate acetate; (ii) causes a decrease of Ca2+ association to cell membranes, so depleting the pools of exchangeable Ca2+ and depressing the 'Ca2+ response' in terms of rise in [Ca2+]i monitored with Quin 2 and of rapid mobilization from cell membranes monitored by chlorotetracycline fluorescence change; (iii) inhibits the Ca2+-activated phospholipid-dependent protein kinase C. The data, discussed in relation to the biochemical mechanisms of the stimulus-response coupling, are compatible with the hypothesis of an involvement of the activation of protein kinase C as key step in the sequence of transduction events for the induction of many neutrophil functions. 相似文献
80.
Covalent cross-linking of vasoactive intestinal peptide (VIP) to its receptor in intact colonic adenocarcinoma cells in culture (HT 29) 总被引:1,自引:0,他引:1
J M Muller J Luis J Fantini B Abadie F Giannellini J Marvaldi J Pichon 《European journal of biochemistry》1985,151(2):411-417
[125I]Monoiodinated vasoactive intestinal peptide (125I-VIP) was cross-linked with human colonic adenocarcinoma cells (HT29 cells) grown as a monolayer using dithiobis(succinimidylpropionate) as cross-linking reagent. The cross-linked polypeptides were separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. A major polypeptide of Mr = 67 000 was characterized and it behaved like a high-affinity binding site for VIP according to the following data. The concentration of native VIP (0.5 nM) giving half-maximum inhibition of 125I-VIP covalent cross-linking with this polypeptide was very similar to that giving half-maximum displacement of 125I-VIP on HT 29 cells (0.6 nM). Glucagon or insulin was unable to inhibit the labelling of the Mr-67 000 component. In our experimental conditions neither specific 125I-VIP binding nor covalent labelling was observed with monolayers of Madin Darby canine kidney epithelial cells (MDCK cells) or African green monkey kidney fibroblasts (Vero cells) while the Mr-67 000 polypeptide was also characterized with human rectal adenocarcinoma cells (HRT 18 cells), known to possess the VIP receptor. Preincubation of HT 29 cells with native VIP at 37 degrees C, before 125I-VIP binding and subsequent cross-linking reaction, decreased the labelling of the Mr-67 000 polypeptide up to 80%. Assuming one molecule of 125I-VIP cross-linked per polypeptide, we have characterized, for the first time, a major polypeptide of Mr = 64 000, which belongs to the high-affinity VIP binding site of an intestinal human cell line. 相似文献