全文获取类型
收费全文 | 1226篇 |
免费 | 79篇 |
专业分类
1305篇 |
出版年
2024年 | 2篇 |
2023年 | 12篇 |
2022年 | 14篇 |
2021年 | 27篇 |
2020年 | 12篇 |
2019年 | 25篇 |
2018年 | 32篇 |
2017年 | 30篇 |
2016年 | 40篇 |
2015年 | 61篇 |
2014年 | 76篇 |
2013年 | 76篇 |
2012年 | 98篇 |
2011年 | 105篇 |
2010年 | 64篇 |
2009年 | 53篇 |
2008年 | 86篇 |
2007年 | 93篇 |
2006年 | 82篇 |
2005年 | 53篇 |
2004年 | 53篇 |
2003年 | 44篇 |
2002年 | 46篇 |
2001年 | 11篇 |
2000年 | 4篇 |
1999年 | 10篇 |
1998年 | 5篇 |
1997年 | 9篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有1305条查询结果,搜索用时 15 毫秒
91.
92.
Gianmauro Numico Antonella Cristofano Alessandro Mozzicafreddo Olga Elisabetta Cursio Pierfrancesco Franco Giulia Courthod Antonio Trogu Alessandra Malossi Mariella Cucchi Zuzana Sirotovà Maria Rosa Alvaro Anna Stella Fulvia Grasso Silvia Spinazzé Nicola Silvestris 《PloS one》2015,10(3)
Background
Cancer patients are frequently admitted to hospital due to acute conditions or refractory symptoms. This occurs through the emergency departments and requires medical oncologists to take an active role. The use of acute-care hospital increases in the last months of life.Patients and methods
We aimed to describe the admissions to a medical oncology inpatient service within a 16-month period with respect to patients and tumor characteristics, and the outcome of the hospital stay.Results
672 admissions of 454 patients were analysed. The majority of admissions were urgent (74.1%), and were due to uncontrolled symptoms (79.6%). Among the chief complaints, dyspnoea occurred in 15.7%, pain in 15.2%, and neurological symptoms in 14.5%. The majority of the hospitalizations resulted in discharge to home (60.6%); in 26.5% the patient died and in 11.0% was transferred to a hospice. Admissions due to symptoms correlated with a longer hospital stay and a higher incidence of in-hospital death.Conclusion
We suggest that hospital use is not necessarily a sign of inappropriately aggressive care: inpatient care is probably an unavoidable step in the cancer trajectory. Optimization of inpatient supportive procedures should be a specific task of modern medical oncology. 相似文献93.
Cristián Tapia Sergio Molina Alvaro Diaz Lilian Abugoch Mario Diaz-Dosque Fernando Valenzuela Mehrdad Yazdani-Pedram 《AAPS PharmSciTech》2010,11(3):1294-1305
The effect of chitosan as internal or external coating on the mesalamine (5-ASA) release from calcium alginate microparticles (CaAl) was studied, and a delayed release of 5-ASA system intended for colonic drug delivery was developed. The external chitosan coating was developed by immersion of wetted CaAl in chitosan solution and the internal coating by mixing 5-ASA with chitosan solution and drying before the preparation of CaAl. Both systems were coated with Acryl-EZE® using combined fluid bed coating and immersion procedure. The results showed that in phosphate medium (pH 7.5), chitosan as 5-ASA coating promotes a quick erosion process accelerating drug release, but chitosan as external coating (CaAlCS) does not increase the T 50 value compared with the microparticles without chitosan (CaAl). Chitosan as internal or external coating was not effective to avoid the quick 5-ASA release in acidic medium (pH 1.2). The presence of β-glucosidase enzymes increases significantly the 5-ASA release for CaAl, while no effect was observed with chitosan as internal or external coating. Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray data revealed that 5-ASA did not form a solid solution but was dispersed in the microparticles. The Acryl-EZE® coating of microparticles was effective because all the formulations showed a low release, less than 15%, of 5-ASA in acid medium at pH 1.2. Significant differences in the percentage of 5-ASA released between formulations were observed in phosphate buffer at pH 6.0. In phosphate buffer at pH 7.2, all the formulations released 100% of 5-ASA. 相似文献
94.
95.
Beatriz Santamaría Alberto Benito-Martin Alvaro Conrado Ucero Luiz Stark Aroeira Ana Reyero María Jesús Vicent Mar Orzáez Angel Celdrán Jaime Esteban Rafael Selgas Marta Ruíz-Ortega Manuel López Cabrera Jesús Egido Enrique Pérez-Payá Alberto Ortiz 《PloS one》2009,4(8)
Background
Inflammation may lead to tissue injury. We have studied the modulation of inflammatory milieu-induced tissue injury, as exemplified by the mesothelium. Peritoneal dialysis is complicated by peritonitis episodes that cause loss of mesothelium. Proinflammatory cytokines are increased in the peritoneal cavity during peritonitis episodes. However there is scarce information on the modulation of cell death by combinations of cytokines and on the therapeutic targets to prevent desmesothelization.Methodology
Human mesothelial cells were cultured from effluents of stable peritoneal dialysis patients and from omentum of non-dialysis patients. Mesothelial cell death was studied in mice with S. aureus peritonitis and in mice injected with tumor necrosis factor alpha and interferon gamma.Tumor necrosis factor alpha and interferon gamma alone do not induce apoptosis in cultured mesothelial cells. By contrast, the cytokine combination increased the rate of apoptosis 2 to 3-fold over control. Cell death was associated with the activation of caspases and a pancaspase inhibitor prevented apoptosis. Specific caspase-8 and caspase-3 inhibitors were similarly effective. Co-incubation with both cytokines also impaired mesothelial wound healing in an in vitro model. However, inhibition of caspases did not improve wound healing and even impaired the long-term recovery from injury. By contrast, a polymeric nanoconjugate Apaf-1 inhibitor protected from apoptosis and allowed wound healing and long-term recovery. The Apaf-1 inhibitor also protected mesothelial cells from inflammation-induced injury in vivo in mice.Conclusion
Cooperation between tumor necrosis factor alpha and interferon gamma contributes to mesothelial injury and impairs the regenerative capacity of the monolayer. Caspase inhibition attenuates mesothelial cell apoptosis but does not facilitate regeneration. A drug targeting Apaf-1 allows protection from apoptosis as well as regeneration in the course of inflammation-induced tissue injury. 相似文献96.
97.
Puentes A García J Ocampo M Rodríguez L Vera R Curtidor H López R Suarez J Valbuena J Vanegas M Guzman F Tovar D Patarroyo ME 《Peptides》2003,24(7):1015-1023
This work determined Plasmodium falciparum merozoite surface protein-8 (MSP-8) regions specifically binding to membrane surface receptors on human erythrocytes. Five high activity binding peptides (HABPs), whose binding to erythrocytes became saturable and sensitive on being treated with neuraminidase and chymotrypsin were identified from the MSP-8 protein. Those amino acids directly involved in interaction with erythrocytes were also determined for each one of the HABPs. Some of them specifically recognized 28, 46, and 73 kDa erythrocyte membrane proteins. Some HABPs inhibited in vitro P. falciparum merozoite invasion of erythrocytes by up to 98%, suggesting the MSP-8 protein's possible role in the invasion process. 相似文献
98.
Marucci L Alpini G Glaser SS Alvaro D Benedetti A Francis H Phinizy JL Marzioni M Mauldin J Venter J Baumann B Ugili L LeSage G 《American journal of physiology. Gastrointestinal and liver physiology》2003,284(2):G290-G301
Bile acids are cytoprotective in hepatocytes by activating phosphatidylinositol-3-kinase (PI3-K) and its downstream signal AKT. Our aim was to determine whether feeding taurocholate to CCl(4)-treated rats reduces cholangiocyte apoptosis and whether this cytoprotective effect is dependent on PI3-K. Cholangiocyte proliferation, secretion, and apoptosis were determined in cholangiocytes from bile duct ligation (BDL), CCl(4)-treated BDL rats, and CCl(4)-treated taurocholate-fed rats. In vitro, we tested whether CCl(4) induces apoptosis and whether loss of cholangiocyte proliferation and secretion is dependent on PI3-K. The CCl(4)-induced cholangiocyte apoptosis and loss of cholangiocyte proliferation and secretion were reduced in CCl(4)-treated rats fed taurocholate. CCl(4)-induced cholangiocyte apoptosis, loss of cholangiocytes secretion, and proliferation were prevented by preincubation with taurocholate. Taurocholate cytoprotective effects were ablated by wortmannin. Taurocholate prevented, in vitro, CCl(4)-induced decrease of phosphorylated AKT protein expression in cholangiocytes. The cytoprotective effects of taurocholate on CCl(4) effects on cholangiocyte proliferation and secretion were abolished by wortmannin. Taurocholate protects cholangiocytes from CCl(4)-induced apoptosis by a PI3-K-dependent mechanism. Bile acids are important in the prevention of drug-induced ductopenia in cholangiopathies. 相似文献
99.
Alvaro Valín Adolfo García-Ocaa Fernando De Miguel Jos L. Sarasa Pedro Esbrit 《Journal of cellular physiology》1997,170(2):209-215
The C-terminal region of parathyroid hormone-related protein (PTHrP) containing the sequence (107–111) appears to be a potent inhibitor of osteoclastic bone resorption. In the present study, we have investigated the effect of human (h)PTHrP (107–139) and hPTHrP (107–111)NH2 on the proliferation of osteoblastic rat osteosarcoma UMR 106 cells. We found that both C-terminal PTHrP peptides, like hPTHrP (1–141), were antimitogenic for these cells, between 1 pM and 10 nM. [Tyr34]hPTHrP (1–34)NH2 was as potent as these peptides but less effective as growth inhibitor in these cells. UMR 106 cells were found to produce and secrete immunoreactive PTHrP. Addition of anti-PTHrP neutralizing antibodies to C- and N-terminal epitopes of PTHrP increased the growth of these cells. Our data suggest that the antiproliferative effect of these C-terminal PTHrP analogs may be independent of cyclic adenosine 3′:5′-monophosphate (cAMP) and mediated by protein kinase C. These findings support an autocrine role of PTHrP in bone metabolism. J. Cell. Physiol. 170:209–215, 1997. © 1997 Wiley-Liss, Inc. 相似文献
100.