全文获取类型
收费全文 | 2958篇 |
免费 | 59篇 |
国内免费 | 283篇 |
出版年
2023年 | 12篇 |
2022年 | 10篇 |
2021年 | 32篇 |
2020年 | 8篇 |
2019年 | 9篇 |
2018年 | 16篇 |
2017年 | 15篇 |
2016年 | 45篇 |
2015年 | 93篇 |
2014年 | 144篇 |
2013年 | 136篇 |
2012年 | 103篇 |
2011年 | 215篇 |
2010年 | 216篇 |
2009年 | 88篇 |
2008年 | 64篇 |
2007年 | 53篇 |
2006年 | 30篇 |
2005年 | 148篇 |
2004年 | 273篇 |
2003年 | 157篇 |
2002年 | 88篇 |
2001年 | 114篇 |
2000年 | 46篇 |
1999年 | 36篇 |
1998年 | 35篇 |
1997年 | 62篇 |
1996年 | 54篇 |
1995年 | 55篇 |
1994年 | 13篇 |
1993年 | 221篇 |
1992年 | 198篇 |
1991年 | 84篇 |
1990年 | 60篇 |
1989年 | 61篇 |
1988年 | 67篇 |
1987年 | 71篇 |
1986年 | 46篇 |
1985年 | 54篇 |
1984年 | 24篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1957年 | 8篇 |
1956年 | 14篇 |
1955年 | 6篇 |
1943年 | 1篇 |
1939年 | 1篇 |
1937年 | 1篇 |
1926年 | 1篇 |
排序方式: 共有3300条查询结果,搜索用时 15 毫秒
991.
992.
993.
Shihori Tanabe Kazuhiko Aoyagi Hiroshi Yokozaki Hiroki Sasaki 《World journal of stem cells》2015,7(1):208-222
AIM: To investigate the genes regulated in mesenchymal stem cells(MSCs) and diffuse-type gastric cancer(GC),gene expression was analyzed. METHODS: Gene expression of MSCs and diffuse-type GC cells were analyzed by microarray. Genes related to stem cells, cancer and the epithelial-mesenchymal transition(EMT) were extracted from human gene lists using Gene Ontology and reference information. Gene panels were generated, and messenger RNA gene expression in MSCs and diffuse-type GC cells was analyzed. Cluster analysis was performed using the NCSS software.RESULTS: The gene expression of regulator of G-protein signaling 1(RGS1) was up-regulated in diffuse-type GC cells compared with MSCs. A panel of stem-cell related genes and genes involved in cancer or the EMT were examined. Stem-cell related genes, such as growth arrest-specific 6, musashi RNA-binding protein 2 and hairy and enhancer of split 1(Drosophila), NOTCH family genes and Notch ligands, such as delta-like 1(Drosophila) and Jagged 2, were regulated.CONCLUSION: Expression of RGS1 is up-regulated, and genes related to stem cells and NOTCH signaling are altered in diffuse-type GC compared with MSCs. 相似文献
994.
Charles Nicaise Dinko Mitrecic Aditi Falnikar Angelo C Lepore 《World journal of stem cells》2015,(2):380-398
Neglected for years, astrocytes are now recognized to fulfill and support many, if not all, homeostatic functionsof the healthy central nervous system(CNS). During neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS) and spinal cord injury(SCI), astrocytes in the vicinity of degenerating areas undergo both morphological and functional changes that might compromise their intrinsic properties. Evidence from human and animal studies show that deficient astrocyte functions or loss-of-astrocytes largely contribute to increased susceptibility to cell death for neurons, oligodendrocytes and axons during ALS and SCI disease progression. Despite exciting advances in experimental CNS repair, most of current approaches that are translated into clinical trials focus on the replacement or support of spinal neurons through stem cell transplantation, while none focus on the specific replacement of astroglial populations. Knowing the important functions carried out by astrocytes in the CNS, astrocyte replacement-based therapies might be a promising approach to alleviate overall astrocyte dysfunction, deliver neurotrophic support to degenerating spinal tissue and stimulate endogenous CNS repair abilities. Enclosed in this review, we gathered experimental evidence that argue in favor of astrocyte transplantation during ALS and SCI. Based on their intrinsic properties and according to the cell type transplanted, astrocyte precursors or stem cell-derived astrocytes promote axonal growth, support mechanisms and cells involved in myelination, are able to modulate the host immune response, deliver neurotrophic factors and provide protective molecules against oxidative or excitotoxic insults, amongst many possible benefits. Embryonic or adult stem cells can even be genetically engineered in order to deliver missing gene products and therefore maximize the chance of neuroprotection and functional recovery. However, before broad clinical translation, further preclinical data on safety, reliability and therapeutic efficiency should be collected. Although several technical challenges need to be overcome, we discuss the major hurdles that have already been met or solved by targeting the astrocyte populationin experimental ALS and SCI models and we discuss avenues for future directions based on latest molecular findings regarding astrocyte biology. 相似文献
995.
Pamela A. Dyson Denis Anthony Brenda Fenton Denise E. Stevens Beatriz Champagne Li-Ming Li Jun Lv Jorge Ramírez Hernández K. R. Thankappan David R. Matthews Community Interventions for Health collaboration 《PloS one》2015,10(4)
Background
Non-communicable disease (NCD) is increasing rapidly in low and middle-income countries (LMIC), and is associated with tobacco use, unhealthy diet and physical inactivity. There is little evidence for up-scaled interventions at the population level to reduce risk in LMIC.Methods
The Community Interventions for Health (CIH) program was a population-scale community intervention study with comparator population group undertaken in communities in China, India, and Mexico, each with populations between 150,000-250,000. Culturally appropriate interventions were delivered over 18-24 months. Two independent cross-sectional surveys of a stratified sample of adults aged 18-64 years were conducted at baseline and follow-up.Results
A total of 6,194 adults completed surveys at baseline, and 6,022 at follow-up. The proportion meeting physical activity recommendations decreased significantly in the control group (C) (44.1 to 30.2%), but not in the intervention group (I) (38.0 to 36.1%), p<0.001. Those eating ≥5 portions of fruit and vegetables daily decreased significantly in C (19.2 to 17.2%), but did not change in I (20.0 to 19.6%,), p=0.013. The proportion adding salt to food was unchanged in C (24.9 to 25.3%) and decreased in I (25.9 to 19.6%), p<0.001. Prevalence of obesity increased in C (8.3 to 11.2%), with no change in I (8.6 to 9.7%,) p=0.092. Concerning tobacco, for men the difference-in-difference analysis showed that the reduction in use was significantly greater in I compared to C (p=0.014)Conclusions
Up-scaling known health promoting interventions designed to reduce the incidence of NCD in whole communities in LMIC is feasible, and has measurable beneficial outcomes on risk factors for NCD, namely tobacco use, diet, and physical inactivity. 相似文献996.
Hyunsuk Kim Jung Nam An Dong Ki Kim Myoung-Hee Kim Ho Kim Yong-Lim Kim Ki Soo Park Yun Kyu Oh Chun Soo Lim Yon Su Kim Jung Pyo Lee CRC for ESRD Investigators 《PloS one》2015,10(6)
The outcomes of peritoneal dialysis (PD) in elderly patients have not been thoroughly investigated. We aimed to investigate the clinical outcomes and risk factors associated with PD in elderly patients. We conducted a prospective observational nationwide adult end-stage renal disease (ESRD) cohort study in Korea from August 2008 to March 2013. Among incident patients (n = 830), patient and technical survival rate, quality of life, and Beck’s Depression Inventory (BDI) scores of elderly PD patients (≥65 years, n = 95) were compared with those of PD patients aged ≤49 years (n = 205) and 50~64 years (n = 192); and elderly hemodialysis (HD) patients (n = 315). The patient death and technical failure were analyzed by cumulative incidence function. Competing risk regressions were used to assess the risk factors for survival. The patient survival rate of elderly PD patients was inferior to that of younger PD patients (P<0.001). However, the technical survival rate was similar (P = 0.097). Compared with elderly HD patients, the patient survival rate did not differ according to dialysis modality (P = 0.987). Elderly PD patients showed significant improvement in the BDI scores, as compared with the PD patients aged ≤49 years (P = 0.003). Low albumin, diabetes and low residual renal function were significant risk factors for the PD patient survival; and peritonitis was a significant risk factor for technical survival. Furthermore, low albumin and hospitalization were significant risk factors of patient survival among the elderly. The overall outcomes were similar between elderly PD and HD patients. PD showed the benefit in BDI and quality of life in the elderly. Additionally, the technical survival rate of elderly PD patients was similar to that of younger PD patients. Taken together, PD may be a comparable modality for elderly ESRD patients. 相似文献
997.
David M. Watson Susan E. Anderson Valerie Olson for the Institute for Land Water Society 《PloS one》2015,10(1)
Reproductive investment is typically considered in terms of size and number of propagules produced. Compared with a thorough understanding of the overall patterns and ecological correlates of avian clutch size, egg size has received less attention and the total effort invested in laying a clutch of eggs is rarely considered. We used clutch volume as an alternative estimate of reproductive investment and present the first class-level analysis of clutch volume in birds using 1,364 randomly-selected species in 204 families. The relationship between body mass and egg volume was very strong (r2 = 0.946), validating previous studies identifying four families (Apterygidae, Pelecanoidiididae, Sternidae and Dromadidiae) with disproportionately large eggs. Clutch volume was also closely related to body mass (r2 = 0.909) and all but one of the taxa with disproportionately large eggs conformed to the overall relationship, their greater egg dimensions compensated by diminished clutch size. The only family which departed significantly from the relationship between body mass and clutch volume was the mound builders (Megapodiidae)—the only group of birds that do not rely on body heat for incubation. Although previously known for laying large clutches of large eggs containing disproportionately large yolks, the remarkable investment of megapodes in reproduction (more than seven times greater than other birds of comparable mass) has been hitherto overlooked. We consider the evolutionary basis and ecological implications of this finding, suggesting that energetic costs associated with incubation act as an upper limit on reproductive output of other birds. We recommend clutch volume as a sensitive, fine-grained measure of reproductive effort for research at a wide range of scales and advocate further analysis of ecological correlates of clutch volume in birds and amniotes generally. 相似文献
998.
Jiri Minarik Petr Pavlicek Ludek Pour Tomas Pika Vladimir Maisnar Ivan Spicka Jiri Jarkovsky Marta Krejci Jaroslav Bacovsky Jakub Radocha Jan Straub Petr Kessler Marek Wrobel Lenka Walterova Michal Sykora Jarmila Obernauerova Lucie Brozova Evzen Gregora Dagmar Adamova Jaromir Gumulec Zdenek Adam Vlastimil Scudla Roman Hajek for the Czech Myeloma Group 《PloS one》2015,10(4)
Objective
Subcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration.Patients and methods
During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly – 63% or twice weekly – 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.Results
The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥2 was present in 20% vs 18% and PN grade ≥3 was present in 6% vs 4%.Conclusions
We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration. 相似文献999.
Jaime Lynn Speiser William M. Lee Constantine J. Karvellas for the US Acute Liver Failure Study Group 《PloS one》2015,10(4)
Background/Aim
Assessing prognosis for acetaminophen-induced acute liver failure (APAP-ALF) patients often presents significant challenges. King’s College (KCC) has been validated on hospital admission, but little has been published on later phases of illness. We aimed to improve determinations of prognosis both at the time of and following admission for APAP-ALF using Classification and Regression Tree (CART) models.Methods
CART models were applied to US ALFSG registry data to predict 21-day death or liver transplant early (on admission) and post-admission (days 3-7) for 803 APAP-ALF patients enrolled 01/1998–09/2013. Accuracy in prediction of outcome (AC), sensitivity (SN), specificity (SP), and area under receiver-operating curve (AUROC) were compared between 3 models: KCC (INR, creatinine, coma grade, pH), CART analysis using only KCC variables (KCC-CART) and a CART model using new variables (NEW-CART).Results
Traditional KCC yielded 69% AC, 90% SP, 27% SN, and 0.58 AUROC on admission, with similar performance post-admission. KCC-CART at admission offered predictive 66% AC, 65% SP, 67% SN, and 0.74 AUROC. Post-admission, KCC-CART had predictive 82% AC, 86% SP, 46% SN and 0.81 AUROC. NEW-CART models using MELD (Model for end stage liver disease), lactate and mechanical ventilation on admission yielded predictive 72% AC, 71% SP, 77% SN and AUROC 0.79. For later stages, NEW-CART (MELD, lactate, coma grade) offered predictive AC 86%, SP 91%, SN 46%, AUROC 0.73.Conclusion
CARTs offer simple prognostic models for APAP-ALF patients, which have higher AUROC and SN than KCC, with similar AC and negligibly worse SP. Admission and post-admission predictions were developed.Key Points
• Prognostication in acetaminophen-induced acute liver failure (APAP-ALF) is challenging beyond admission• Little has been published regarding the use of King’s College Criteria (KCC) beyond admission and KCC has shown limited sensitivity in subsequent studies• Classification and Regression Tree (CART) methodology allows the development of predictive models using binary splits and offers an intuitive method for predicting outcome, using processes familiar to clinicians• Data from the ALFSG registry suggested that CART prognosis models for the APAP population offer improved sensitivity and model performance over traditional regression-based KCC, while maintaining similar accuracy and negligibly worse specificity• KCC-CART models offered modest improvement over traditional KCC, with NEW-CART models performing better than KCC-CART particularly at late time points 相似文献1000.
Jenni Hislop Temitope E. Adewuyi Luke D. Vale Kirsten Harrild Cynthia Fraser Tara Gurung Douglas G. Altman Andrew H. Briggs Peter Fayers Craig R. Ramsay John D. Norrie Ian M. Harvey Brian Buckley Jonathan A. Cook for the DELTA group 《PLoS medicine》2014,11(5)