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21.
Huo Y Guo X Li H Xu H Halim V Zhang W Wang H Fan YY Ong KT Woo SL Chapkin RS Mashek DG Chen Y Dong H Lu F Wei L Wu C 《The Journal of biological chemistry》2012,287(25):21492-21500
Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. 相似文献
22.
《Phytomedicine》2014,21(7):970-977
Chemotherapy is the recommended treatment for advanced-stage cancers. However, the emergence of multidrug resistance (MDR), the ability of cancer cells to become simultaneously resistant to different drugs, limits the efficacy of chemotherapy. Previous studies have shown that herbal medicine or natural food may be feasible for various cancers as potent chemopreventive drug. This study aims to explore the capablility of reversing the multidrug resistance of docetaxel (DOC)-resistant A549 cells (A549/D16) of psoralen and the underlying mechanisms. In this study, results showed that the cell viability of A549/D16 subline is decreased when treated with psoralen plus DOC, while psoralen has no effect on the cell proliferation on A549 and A549/D16 cells. Furthermore, mRNA and proteins levels of ABCB1 were decreased in the presence of psoralen, while decreased ABCB1 activity was also revealed by flow cytometry. Based on these results, we believe that psoralen may be feasible for reversing the multidrug resistance by inhibiting ABCB1 gene and protein expression. Such inhibition will lead to a decrease in ABCB1 activity and anti-cancer drug efflux, which eventually result in drug resistance reversal and therefore, sensitizing drug-resistant cells to death in combination with chemotherapeutic drugs. 相似文献
23.
Herr I Gassler N Friess H Büchler MW 《Apoptosis : an international journal on programmed cell death》2007,12(2):271-291
More than a quarter of a century ago, the phenomenon of glucocorticoid-induced apoptosis in the majority of hematological
cells was first recognized. More recently, glucocorticoid-induced antiapoptotic signaling associated with apoptosis resistance
has been identified in cells of epithelial origin, most of malignant solid tumors and some other tissues. Despite these huge
amount of data demonstrating differential pro- and anti-apoptotic effects of glucocortioids, the underlying mechanisms of
cell type specific glucocorticoid signaling are just beginning to be described. This review summarizes our present understanding
of cell type-specific pro- and anti-apoptotic signaling induced by glucocorticoids. In the first section we give a summary
and update of known glucocorticoid-induced pathways mediating apoptosis in hematological cells. We shortly introduce mechanisms
of glucocorticoid resistance of hematological cells. We highlight and discuss the emerging molecular evidence of a general
induction of survival signaling in epithelial cells and carcinoma cells by glucocorticoids. We provide a model for glucocorticoid-induced
resistance in cells growing in a tissue formation. Thus, attachment to the extracellular matrix and cell-cell contacts typical
for e.g. epithelial and tumor cells may be crucially involved in switching the balance of several interacting pathways to
survival upon treatment with glucocorticoids. 相似文献
24.
A. Wiese M. Münstermann T. Gutsmann B. Lindner K. Kawahara U. Zähringer U. Seydel 《The Journal of membrane biology》1998,162(2):127-138
We have studied the interaction of the polycationic peptide antibiotic polymyxin B (PMB) with asymmetric planar bilayer membranes
via electrical measurements. The bilayers were of different compositions, including those of the lipid matrices of the outer
membranes of various species of Gram-negative bacteria. One leaflet, representing the bacterial inner leaflet, consisted of
a phospholipid mixture (PL; phosphatidylethanolamine, -glycerol, and diphosphatidylglycerol in a molar ratio of 81:17:2).
The other (outer) leaflet consisted either of lipopolysaccharide (LPS) from deep rough mutants of PMB-sensitive (Escherichia coli F515) or -resistant strains (Proteus mirabilis R45), glycosphingolipid (GSL-1) from Sphingomonas paucimobilis IAM 12576, or phospholipids (phosphatidylglycerol, diphytanoylphosphatidylcholine). In all membrane systems, the addition
of PMB to the outer leaflet led to the induction of current fluctuations due to transient membrane lesions. The minimal PMB
concentration required for the induction of the lesions and their size correlated with the charge of the lipid molecules.
In the membrane system resembling the lipid matrix of a PMB-sensitive strain (F515 LPS/PL), the diameters of the lesions were
large enough (d= 2.4 nm ± 8%) to allow PMB molecules to permeate (self-promoted transport), but in all other systems they were too small.
A comparison of these phenomena with membrane effects induced by detergents (dodecyltriphenylphosphonium bromide, dodecyltrimethylammonium
bromide, sodiumdodecylsulfate) revealed a detergent-like mechanism of the PMB-membrane interaction.
Received: 16 September 1997/Revised: 25 November 1997 相似文献
25.
Wenhui Zhao Xinmei Kang Shi Jin Changjie Lou 《Biochemical and biophysical research communications》2009,380(3):699-439
Acquired resistance to tamoxifen has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this condition has not been completely elucidated. In this study, a tamoxifen-resistant (Tam-R) MCF-7 breast cancer cell line was developed to mimic the occurrence of acquired tamoxifen resistance as seen in clinical practice. Increased expression levels of HER1, HER2 and the estrogen receptor (ER)-AIB1 complex were found in tamoxifen-resistant cells. EGF stimulation and gefitinib inhibition experiments further demonstrated that HER1/HER2 signaling and AIB1 were involved in the proliferation of cells that had acquired Tam resistance. However, when AIB1 was silenced with AIB1-siRNA in Tam-R cells, the cell growth stimulated by the HER1/HER2 signaling pathway was significantly reduced, and the cells were again found to be inhibited by tamoxifen. These results suggest that the AIB1 protein could be a limiting factor in the HER1/HER2-mediated hormone-independent growth of Tam-R cells. Thus, AIB1 may be a new therapeutic target, and the removal of AIB1 may decrease the crosstalk between ER and the HER1/HER2 pathway, resulting in the restoration of tamoxifen sensitivity in tamoxifen-resistant cells. 相似文献
26.
目的:探索AXL在肺腺癌细胞(Lung adenocarcinoma cell, LAC)EGFR-TKIs获得性耐药中的作用,为肺癌临床治疗和新型药物的研发提供实验依据。方法:构建EGFR-TKIs获得性耐药的肺腺癌模型并通过CCK-8法检测耐药株对肺腺癌靶向治疗药物吉非替尼(Gefitinib)、厄洛替尼(Erlotinib)和奥希替尼(Osimertinib)的敏感性。基于基因组学分析筛选出潜在的克服耐药的靶点AXL,通过Western blot和qRT-PCR技术检测AXL的表达情况,并同时检测上皮-间质转化(Epithelial-mesenchymal transition,EMT)分子标志物。R428是AXL的小分子抑制剂,通过CCK-8法、Transwell以及划痕实验等探究靶向AXL对肺腺癌亲本及耐药株增殖和迁移能力的影响。结果:AXL在构建的耐药株中显著高表达,其蛋白表达水平上调15-20倍(P0.001),m RNA水平上调2-5倍(P0.01);EGFR-TKIs耐药株发生上皮间质转化(EMT);靶向AXL选择性抑制耐药株的增殖能力并且恢复了耐药株对EGFR-TKIs的敏感性(P0.001);靶向AXL显著抑制耐药株增强的迁移能力,与亲本株相比最高抑制率可达80%左右(P0.001)。结论:用遗传学和药理学手段靶向AXL可以显著逆转肺腺癌对EGFR-TKIs耐药,逆转耐药株所增强的迁移等肿瘤生物学特征,对克服EGFR-TKIs获得性耐药有着重要的临床治疗价值以及转化医学前景。 相似文献
27.
We compared growth rate, cell glucose turnover and expression of ATP-binding-cassette (ABC) transporters in Leishmania amazonensis (LTB0016; LTB) versus LTB(160) selected for resistance against the ABC transporter blocker glibenclamide. Additionally, we evaluated the influence of drug-resistance on Leishmania sensitivity against 2-mercaptoacetate and 2-deoxyglucose. Our data demonstrate that (1) LTB(160) and LTB constitutively express ABC transporters for neutral substrates, (2) glibenclamide resistance induces the expression of organic anion ABC transporters, members of the drug resistance associated transporters subfamily, (3) LTB(160) parasites use less glucose as energy substrate and exhibit a slower glucose uptake than LTB cells, and (4) LTB(160) parasites are less sensitive to 2-mercaptoacetate and 2-deoxyglucose than the glibenclamide-sensitive Leishmania LTB. Together these and previous results indicate that the metabolic adaptations expressed in drug-resistant LTB(160) differ from those described for mammalian drug resistant cells and constitute general mechanisms that underlie drug resistance in Leishmania and may be helpful for identifying alternative strategies to circumvent drug resistance in leishmaniasis. 相似文献
28.
Liliya A. Pylypenko Dina D. Sigareva 《Archives Of Phytopathology And Plant Protection》2013,46(5):283-291
In researching the function of the system of Globodera rostochiensis resistant plants, we observed the development of G. rostochiensis (pathotype Ro 1) in glasshouse experiments. For a period of two months, we determined the qualities (the presence of juveniles stages) and quantities (the ratio of ages and the duration of periods of development of the juveniles stages) of parameters of nematodes development on potato wild and cultured species as well as hybrids. Comparative analysis of the rate and specifics of ontogenetic changes in G. rostochensis (Ro 1) during parasitism in the boundaries of specific plant groups, allowed us to assert the following types of resistance to G. rostochiensis: antixenosis, antibiosis, hypersensitive response. 相似文献
29.
Kozlova NI Morozevich GE Shtil AA Berman AE 《Biochemical and biophysical research communications》2004,316(4):1173-1177
We studied whether acquisition of multidrug resistance (MDR) by tumor cells can alter their integrin profile and malignant behavior. Hamster fibroblast cell line HET-SR-2SC-LNM was selected for MDR, yielding the 2SC/20 subline. Compared with the parental cells, the 2SC/20 subline weakly adhered to denatured collagen (dCol) which correlated with decreased expression of alphavbeta3, a dCol receptor. Importantly, 2SC/20 subline demonstrated significantly decreased activity of collagenase MMP-2, lower ability to invade Matrigel, and attenuated metastasis in syngeneic animals. We provide evidence for the first time that selection for MDR can be associated with down-regulation of alphavbeta3 integrin, supporting our recent proof of the pro-apoptotic role of this integrin (Oncogene 20 (2001) 4710). Lack of alphavbeta3 expression may link cell survival under toxic conditions with decreased malignancy of the resulting drug resistant tumor. 相似文献
30.
陆地棉品种和骨干品系黄萎病抗性鉴定 总被引:1,自引:0,他引:1
选育和推广抗病品种是防治陆地棉黄萎病的主要措施,为了早日实现多类型、多区域大面积抗病品种的应用,本研究选取107份遗传背景差异较大的种质,利用河北省农林科学院棉花研究所小安舍试验站黄萎病病圃进行了3年黄萎病抗性重复鉴定。鉴定得到抗病品系8个,占7.5%;耐病品种(系)20个,占18.7%。本研究表明,当前被作为育种亲本的抗病品系还太少,需要深入开展抗病遗传机制,以及与其他经济性状协同改良的关系,为陆地棉抗病育种提供理论指导;达到抗病或接近抗病水平的大部分品种(系)来自于海陆野远缘后代,具有外源基因血统,证明了远缘杂交是陆地棉黄萎病抗性改良的有效手段。 相似文献