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111.
ΔfosB是fosB基因的自然截短型,稳定存在于许多组织中,在脂肪细胞和成骨细胞的形成和分化中起到重要作用。ΔFosB蛋白可能与钙在骨和乳腺中的代谢有关,并且调控钙从骨向乳腺转移的信号通路。将奶山羊的ΔfosB基因亚克隆到pET32a载体得到pET32a-ΔfosB原核表达载体,IPTG诱导其在大肠杆菌中表达,纯化融合蛋白免疫兔子制备多克隆抗体。ELISA检测显示抗体效价达1:51200,Western blotting结果显示制备的抗体能特异性检测原核表达的ΔFosB蛋白以及在HEK-293细胞中表达的ΔFosB蛋白。进一步的组织差异表达检测表明ΔFosB在山羊的乳腺、骨髓、脑髓、肌肉、心脏、肝和肺组织中均有表达。 相似文献
112.
Overexpression of glycerol-3-phosphate acyltransferase gene improves chilling tolerance in tomato 总被引:1,自引:0,他引:1
A tomato (Lycopersicon esculentum Mill.) glycerol-3-phosphate acyltransferase gene (LeGPAT) was isolated. The deduced amino acid sequence revealed that LeGPAT contained four acyltransferase domains, showing high identities with GPAT in other plant species. A GFP fusion protein of LeGPAT was targeted to chloroplast in cowpea mesophyll protoplast. RNA gel blot showed that the mRNA accumulation of LeGPAT in the wild type (WT) was induced by chilling temperature. Higher expression levels were observed when tomato leaves were exposed to 4 degrees C for 4 h. RNA gel and western blot analysis confirmed that the sense gene LeGPAT was transferred into the tomato genome and overexpressed under the control of 35S-CaMV. Although tomato is classified as a chilling-sensitive plant, LeGPAT exhibited selectivity to 18:1 over 16:0. Overexpression of LeGPAT increased total activity of LeGPAT and cis-unsaturated fatty acids in PG in thylakoid membrane. Chilling treatment induced less ion leakage from the transgenic plants than from the WT. The photosynthetic rate and the maximal photochemical efficiency of PS II (Fv/Fm) in transgenic plants decreased more slowly during chilling stress and recovered faster than in WT under optimal conditions. The oxidizable P700 in both WT and transgenic plants decreased obviously at chilling temperature under low irradiance, but the oxidizable P700 recovered faster in transgenic plants than in the WT. These results indicate that overexpression of LeGPAT increased the levels of PG cis-unsaturated fatty acids in thylakoid membrane, which was beneficial for the recovery of chilling-induced PS I photoinhibition in tomato. 相似文献
113.
Human anti-CXCR4 antibodies undergo VH replacement, exhibit functional V-region sulfation, and define CXCR4 antigenic heterogeneity 总被引:1,自引:0,他引:1
Xu C Sui J Tao H Zhu Q Marasco WA 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(4):2408-2418
The chemokine receptor CXCR4 and its ligand stromal-derived factor-1 (SDF-1/CXCL12) are essential for many biological processes and various pathological conditions. However, the relationship between CXCR4 antigenic structure and SDF-1-mediated biological responses is poorly understood. In this report, a panel of human anti-CXCR4 Abs were isolated and used to explore CXCR4 antigenic heterogeneity and function. Multiple fixed CXCR4 antigenic isoforms were detected on the surface of hemopoietic cells. Epitope mapping studies demonstrated the complex nature of the surface-exposed CXCR4 epitopes. Ab-mediated inhibition of chemotaxis correlated strongly with binding affinity, epitope recognition, as well as the level of CXCR4 isoform expression. In addition, detailed genetic analyses of these Abs showed evidence of V(H) replacement. Importantly, structural and biochemical studies demonstrated tyrosine sulfation in novel regions of the V genes that contributed bidirectionally to the binding activity of the Abs. These data provide the first evidence that functional tyrosine sulfation occurs in self-reactive Abs and suggest a potential new mechanism that may contribute to the pathogenesis of Ab-mediated autoimmune disease. These Abs also provide valuable tools to explore the selective in vivo targeting of CXCR4 isoforms that may be preferentially expressed in certain disease states and involved in steady-state CXCR4-SDF-1 homeostasis. 相似文献
114.
SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis 总被引:11,自引:0,他引:11
Kim D Nguyen MD Dobbin MM Fischer A Sananbenesi F Rodgers JT Delalle I Baur JA Sui G Armour SM Puigserver P Sinclair DA Tsai LH 《The EMBO journal》2007,26(13):3169-3179
A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention. 相似文献
115.
Lanter JC Fiordeliso JJ Alford VC Zhang X Wells KM Russell RK Allan GF Lai MT Linton O Lundeen S Sui Z 《Bioorganic & medicinal chemistry letters》2007,17(9):2545-2548
Through an in vivo screening model, we developed the in vivo SAR of beta-alkylthio indolyl carbinols. Through these efforts we identified a compound with potent oral in vivo efficacy in both immature and mature rat prostate weight reduction models and in a murine xenograft prostate cancer model. 相似文献
116.
A series of novel substituted purines containing a side chain with a terminal amino or guanidyl group were designed and synthesized as HIV-1 Tat-TAR inhibitors. All the compounds could effectively block the TAR transactivation in human 293T cells with the CAT expression percentage ranging from 34.4% to 65.7% and showed high antiviral effects with low cytotoxicities in inhibiting the formation of SIV-induced syncytium in CEM174 cells. Molecular modeling studies by Auto-dock process suggest that the compounds bind to TAR RNA in two different modes. 相似文献
117.
Allan G Lai MT Sbriscia T Linton O Haynes-Johnson D Bhattacharjee S Dodds R Fiordeliso J Lanter J Sui Z Lundeen S 《The Journal of steroid biochemistry and molecular biology》2007,103(1):76-83
The pharmacological activity of JNJ-26146900 is described. JNJ-26146900 is a nonsteroidal androgen receptor (AR) ligand with tissue-selective activity in rats. The compound was evaluated in in vitro and in vivo models of AR activity. It binds to the rat AR with a K(i) of 400nM and acts as a pure androgen antagonist in an in vitro cell-based assay. Its in vitro profile is similar to the androgen antagonist bicalutamide (Casodex). In intact rats, JNJ-26146900 reduces ventral prostate weight with an oral potency (ED(50)) of 20-30mg/kg, again comparable to that of bicalutamide. JNJ-26146900 prevented prostate tumor growth in the Dunning rat model, maximally inhibiting growth at a dose of 10mg/kg. It slowed tumor growth significantly in a CWR22-LD1 mouse xenograft model of human prostate cancer. It was tested in aged male rats for its ability to prevent bone loss and loss of lean body mass following orchidectomy. After 6 weeks of dosing, bone volume decreased by 33% in orchidectomized versus intact vehicle-treated rats with a probability (P) of less than 0.05, as measured by micro-computerized tomography analysis. At a dose of 30mg/kg, JNJ-26146900 significantly reduced castration-induced tibial bone loss as indicated by the following parameters: bone volume, trabecular connectivity, trabecular number and spacing between trabeculae. Bone mineral density decreased from 229+/-34mg/cm(3) of hydroxyapatite to 166+/-26mg/cm(3) following orchidectomy, and was maintained at 194+/-20mg/cm(3) with JNJ-26146900 treatment (P<0.05 relative to orchidectomy alone). Using magnetic resonance imaging, the compound was found to partially prevent orchidectomy-induced loss of lean body mass. Our data show that selective androgen receptor modulators (SARMs) have the potential for anabolic effects on bone and muscle while maintaining therapeutic efficacy in prostate cancer. 相似文献
118.
Kang FA Guan J Jain N Allan G Linton O Tannenbaum P Chen X Xu J Zhu P Gunnet J Demarest K Lundeen S Sui Z 《Bioorganic & medicinal chemistry letters》2007,17(9):2531-2534
Efficient parallel synthesis of novel 7-oxa-steroids 4 has been achieved from the key intermediate 3 via a one-pot four-step sequence. oxa-Steroids 4 with various ortho-, meta-, and para-monosubstituents on the phenyl ring, as well as disubstituted phenyl and heterocycles, were evaluated for progesterone receptor (PR) and glucocorticoid receptor (GR) antagonist activities. SAR study demonstrated that the para-fluorinated substituents on the phenyl ring not only increased the potency for PR in a T47D cell functional assay, but also improved the selectivity over GR in an A549 cell functional assay. The para-fluorophenyl oxa-steroid 4l and the para-trifluoromethylphenyl oxa-steroid 4p were found to be remarkably more potent and more selective PR antagonists than mifepristone, with subnanomolar potency and about 140-fold selectivity over GR. Molecular modeling of the oxa-steroid bound to PR provided meaningful insight for the SAR study. oxa-Steroids 4a and 4b were found to be more efficacious than mifepristone in vivo in a rat uterine complement C3 assay via the oral route, although they were less than or equally potent to mifepristone in the T47D assay. 相似文献
119.
Kang FA Allan G Guan J Jain N Linton O Tannenbaum P Xu J Zhu P Gunnet J Chen X Demarest K Lundeen S Sui Z 《Bioorganic & medicinal chemistry letters》2007,17(4):907-910
A novel series of oxa-steroids 6 derived from (8S, 13S, 14R)-7-oxa-estra-4,9-diene-3,17-dione 1 have been synthesized and identified as potent and selective progesterone receptor antagonists. These novel oxa-steroids showed similar potency to mifepristone. Preliminary SAR study resulted in the most potent 17-phenylethynyl oxa-steroid 6i wih an IC(50) of 1.4nM. In contrast to the equipotent mifepristone toward the progesterone receptor (PR) and glucocorticoid receptor (GR), compound 6i had over 200-fold selectivity for PR over GR. 相似文献
120.
模拟大气CO2浓度和温度升高对亚高山冷杉(Abies faxoniana)林土壤酶活性的影响 总被引:1,自引:0,他引:1
采用控制环境生长室研究了川西亚高山森林生态系统中与C、N、P循环有关的土壤转化酶、脲酶、硝酸还原酶和酸性磷酸酶活性的月动态及其对模拟大气CO2浓度增加、温度升高以及交互作用的动态响应。在一个生长季节内,土壤有机层和矿质土壤层的转化酶、脲酶、硝酸还原酶和酸性磷酸酶的活性高峰均出现在温度较高的夏季。其中,土壤有机层的转化酶活性高峰出现在6月份,但土壤矿质层的转化酶活性高峰出现在7月份,土壤有机层和矿质土壤层的脲酶和酸性磷酸酶的活性高峰均出现在7月份,而硝酸还原酶的活性高峰均出现在8月份。升高大气CO2浓度处理(EC)对土壤有机层和矿质土壤层的转化酶、脲酶、硝酸还原酶和酸性磷酸酶活性没有显著影响。升高温度处理(ET)显著增加了土壤有机层和矿质土壤层的酶活性,并且土壤有机层的转化酶、硝酸还原酶和脲酶活性增加更显著。大气CO2浓度增加和温度升高之间的交互作用(ECT)对土壤有机层和矿质土壤层酶活性的影响主要是温度升高引起的。 相似文献