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排序方式: 共有1451条查询结果,搜索用时 15 毫秒
91.
Joseph S. Baxter Nichola Johnson Katarzyna Tomczyk Andrea Gillespie Sarah Maguire Rachel Brough Laura Fachal Kyriaki Michailidou Manjeet K. Bolla Qin Wang Joe Dennis Thomas U. Ahearn Irene L. Andrulis Hoda Anton-Culver Natalia N. Antonenkova Volker Arndt Kristan J. Aronson Annelie Augustinsson Olivia Fletcher 《American journal of human genetics》2021,108(7):1190-1203
92.
Olivia Majer Christelle Bourgeois Florian Zwolanek Caroline Lassnig Dontscho Kerjaschki Matthias Mack Mathias Müller Karl Kuchler 《PLoS pathogens》2012,8(7)
Invasive fungal infections by Candida albicans (Ca) are a frequent cause of lethal sepsis in intensive care unit patients. While a contribution of type I interferons (IFNs-I) in fungal sepsis remains unknown, these immunostimulatory cytokines mediate the lethal effects of endotoxemia and bacterial sepsis. Using a mouse model lacking a functional IFN-I receptor (Ifnar1−/−), we demonstrate a remarkable protection against invasive Ca infections. We discover a mechanism whereby IFN-I signaling controls the recruitment of inflammatory myeloid cells, including Ly6Chi monocytes and neutrophils, to infected kidneys by driving expression of the chemokines CCL2 and KC. Within kidneys, monocytes differentiate into inflammatory DCs but fail to functionally mature in Ifnar1−/− mice, as demonstrated by the impaired upregulation of the key activation markers PDCA1 and iNOS. The increased activity of inflammatory monocytes and neutrophils results in hyper-inflammation and lethal kidney pathology. Pharmacological diminution of monocytes and neutrophils by treating mice with pioglitazone, a synthetic agonist of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ), strongly reduces renal immunopathology during Ca infection and improves mouse survival. Taken together, our data connect for the first time the sepsis-promoting functions of IFNs-I to the CCL2-mediated recruitment and the activation of inflammatory monocytes/DCs with high host-destructing potency. Moreover, our data demonstrate a therapeutic relevance of PPAR-γ agonists for microbial infectious diseases where inflammatory myeloid cells may contribute to fatal tissue damage. 相似文献
93.
Alex A. Pollen Aparna Bhaduri Madeline G. Andrews Tomasz J. Nowakowski Olivia S. Meyerson Mohammed A. Mostajo-Radji Elizabeth Di Lullo Beatriz Alvarado Melanie Bedolli Max L. Dougherty Ian T. Fiddes Zev N. Kronenberg Joe Shuga Anne A. Leyrat Jay A. West Marina Bershteyn Craig B. Lowe Bryan J. Pavlovic Arnold R. Kriegstein 《Cell》2019,176(4):743-756.e17
94.
In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer 下载免费PDF全文
Ran Wei Janet Pik Ching Wong Peng Lyu Xinping Xi Olivia Tong Shu‐Dong Zhang Hiu Fung Yuen Senji Shirasawa Hang Fai Kwok 《Journal of cellular and molecular medicine》2018,22(9):4097-4105
Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progression; however, the mechanism of OPN‐induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage‐independent growth, cell migration and invasion in KRAS gene mutant cells but to a lesser extent in KRAS wild‐type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E‐cadherin in KRAS mutant cells. In human CRC specimens, a high‐level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E‐cadherin expression. Furthermore, we have found that 15 genes were co‐upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene signature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer. 相似文献
95.
Olivia Harvey 《New genetics and society》2013,32(2):125-136
Abstract Over 12 months prior to the recent United Nations decision to defer a decision about what type of international treaty should be developed in the global stem-cell research and human cloning debate, the Federal Parliament of Australia passed two separate pieces of legislation relating to both these concerns. After a five-year long process of community consultation, media spectacle and parliamentary debate, reproductive cloning has been banned in Australia and only embryos considered to be excess to assisted reproductive technologies in existence on the 5th of April 2002 are currently valid research material. This paper argues that underpinning both pieces of legislation is a profound belief in the disruptive potential of all types of human cloning for the very nature and integrity of human species being. A belief, moreover, that is based on a presumption that it is apparently possible to conceptualise what being human even means for all Australians. 相似文献
96.
97.
Olivia L. Mooren Joanna Kim Jinmei Li John A. Cooper 《The Journal of biological chemistry》2015,290(30):18796-18805
Endothelial cells (ECs) form a monolayer that serves as a barrier between the blood and the underlying tissue. ECs tightly regulate their cell-cell junctions, controlling the passage of soluble materials and immune cells across the monolayer barrier. We studied the role of N-WASP, a key regulator of Arp2/3 complex and actin assembly, in EC monolayers. We report that N-WASP regulates endothelial monolayer integrity by affecting the organization of cell junctions. Depletion of N-WASP resulted in an increase in transendothelial electrical resistance, a measure of monolayer integrity. N-WASP depletion increased the width of cell-cell junctions and altered the organization of F-actin and VE-cadherin at junctions. N-WASP was not present at cell-cell junctions in monolayers under resting conditions, but it was recruited following treatment with sphingosine-1-phosphate. Taken together, our results reveal a novel role for N-WASP in remodeling EC junctions, which is critical for monolayer integrity and function. 相似文献
98.
Tubulin dimer dissociation and proteolytic accessibility 总被引:2,自引:0,他引:2
The alpha and beta subunits of the tubulin dimer each possess a distal C-terminal subtilisin cleavage site which, when cleaved, releases an acidic, small peptide. In addition, each possesses an internal site, cleaved by trypsin in alpha and chymotrypsin in beta, which connects the amino and carboxyl structural domains. A model of the dimer is presented which suggests that the beta C-terminal subtilisin site may be more accessible in the monomer than in the dimer. Kinetics of cleavage at this site on the dimer yield straight-line plots of log (undigested fraction) versus time, from which pseudo-first-order rate constants are obtained. Temperature effects on the rate constant are due to changes in the activity of subtilisin, not to temperature-induced unfolding around this site. The rate constant is proportional to the subtilisin/tubulin ratio, whether this is varied by changing the concentration of subtilisin or of tubulin. However, if the rate constant increases due to decreasing tubulin concentration, the extrapolated zero time intercept decreases. The decrease in zero time intercept is interpreted as being due to the appearance of a rapidly digested fraction upon dilution of tubulin. The increase observed in this fast fraction with dilution of tubulin is fully reversible upon reconcentration. It is suggested that this fast fraction represents monomeric beta-tubulin and the concentration dependence of this fast fraction indicates a dissociation constant of about 1.5 X 10(-7) M. 相似文献
99.
100.
Dybzinski Ray Taylor Natalie Prosser Megan Niosi Olivia Demo Madeline Kilbane Erin 《Plant Ecology》2021,222(8):977-991
Plant Ecology - Understanding resource uptake as a function of fine-root mass is important for both basic ecological theory and applied biogeochemical cycling models. We measured plant population... 相似文献