全文获取类型
收费全文 | 14064篇 |
免费 | 1373篇 |
国内免费 | 15篇 |
出版年
2024年 | 11篇 |
2023年 | 119篇 |
2022年 | 269篇 |
2021年 | 491篇 |
2020年 | 233篇 |
2019年 | 337篇 |
2018年 | 380篇 |
2017年 | 364篇 |
2016年 | 560篇 |
2015年 | 847篇 |
2014年 | 840篇 |
2013年 | 948篇 |
2012年 | 1193篇 |
2011年 | 1170篇 |
2010年 | 747篇 |
2009年 | 581篇 |
2008年 | 822篇 |
2007年 | 829篇 |
2006年 | 656篇 |
2005年 | 645篇 |
2004年 | 588篇 |
2003年 | 508篇 |
2002年 | 519篇 |
2001年 | 203篇 |
2000年 | 229篇 |
1999年 | 179篇 |
1998年 | 121篇 |
1997年 | 59篇 |
1996年 | 77篇 |
1995年 | 71篇 |
1994年 | 57篇 |
1993年 | 48篇 |
1992年 | 84篇 |
1991年 | 74篇 |
1990年 | 71篇 |
1989年 | 66篇 |
1988年 | 47篇 |
1987年 | 38篇 |
1986年 | 49篇 |
1985年 | 55篇 |
1984年 | 42篇 |
1983年 | 29篇 |
1982年 | 21篇 |
1981年 | 37篇 |
1980年 | 21篇 |
1979年 | 23篇 |
1978年 | 22篇 |
1977年 | 18篇 |
1976年 | 12篇 |
1972年 | 7篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Katrina J. Curtis Katie A. O’Brien Rebecca J. Tanner Juliet I. Polkey Magdalena Minnion Martin Feelisch Michael I. Polkey Lindsay M. Edwards Nicholas S. Hopkinson 《PloS one》2015,10(12)
Background
Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD.Methods
We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nitrate) or placebo (nitrate-depleted beetroot juice) 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage.Results
21 subjects successfully completed the study (age 68±7years; BMI 25.2±5.5kg/m2; FEV1 percentage predicted 50.1±21.6%; peak VO2 18.0±5.9ml/min/kg). Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7±8mmHg nitrate vs. -1±8mmHg placebo; p = 0.008). Median endurance time did not differ significantly; nitrate 5.65 (3.90–10.40) minutes vs. placebo 6.40 (4.01–9.67) minutes (p = 0.50). However, isotime oxygen consumption (VO2) was lower following nitrate supplementation (16.6±6.0ml/min/kg nitrate vs. 17.2±6.0ml/min/kg placebo; p = 0.043), and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve.Conclusions
Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype.Trial Registration
ISRCTN Registry ISRCTN66099139 相似文献992.
Sumanta Kumar Pal Yulan Ingrid Lin Bertram Yuh Kara DeWalt Austin Kazarian Nicholas Vogelzang Rebecca A. Nelson 《PloS one》2015,10(8)
Background
Second-line therapy is frequently utilized for metastatic urothelial carcinoma, but there are limited data to guide this approach. While an assessment of overall survival based on registry data may not capture the impact of second- and third-line therapies on clinical outcome, this may be reflected in relative conditional survival (RCS).Methods
Patients with stage IV urothelial carcinoma diagnosed from 1990–2010 were identified from the Surveillance, Epidemiology and End Results (SEER) dataset. The association of clinicopathologic variables with disease specific survival (DSS) was explored through univariate and multivariate analyses. DSS in subgroups divided by time period (1990–2000 v 2001–2010) was compared using the Kaplan-Meier method and log-rank test. One-year RCS at annual landmarks up to 5 years was compared in subgroups divided by time period.Results
Of 261,987 patients diagnosed with urothelial carcinoma from 1990–2010, 3,110 patients met criteria for the current analysis. Characteristics of patients diagnosed between 1990 and 2000 (n = 810) and 2001 to 2010 (n = 2,300) were similar and there was no significant difference in DSS between the two groups. On multivariate analysis, older age (age ≥ 80) was associated with shorter DSS (HR 1.79, 95%CI 1.48–2.15), but no association was found between time period of diagnosis and outcome. One-year RCS improved substantially through successive annual landmarks up to 5 years, but no differences were seen in subgroups divided by time of diagnosis.Conclusions
No difference in RCS was observed amongst patients with stage IV urothelial carcinoma diagnosed from 1990–2000 and 2001–2010. A lack of difference in RCS (more so than cumulative DSS) may reflect a lack of progress in salvage therapies for the disease. 相似文献993.
Wei Chen Shaozhen He Degao Liu Gunvant B. Patil Hong Zhai Feibing Wang Troy J. Stephenson Yannan Wang Bing Wang Babu Valliyodan Henry T. Nguyen Qingchang Liu 《PloS one》2015,10(9)
Sweetpotato highly produces carotenoids in storage roots. In this study, a cDNA encoding geranylgeranyl phyrophosphate synthase (GGPS), named IbGGPS, was isolated from sweetpotato storage roots. Green fluorescent protein (GFP) was fused to the C-terminus of IbGGPS to obtain an IbGGPS-GFP fusion protein that was transiently expressed in both epidermal cells of onion and leaves of tobacco. Confocal microscopic analysis determined that the IbGGPS-GFP protein was localized to specific areas of the plasma membrane of onion and chloroplasts in tobacco leaves. The coding region of IbGGPS was cloned into a binary vector under the control of 35S promoter and then transformed into Arabidopsis thaliana to obtain transgenic plants. High performance liquid chromatography (HPLC) analysis showed a significant increase of total carotenoids in transgenic plants. The seeds of transgenic and wild-type plants were germinated on an agar medium supplemented with polyethylene glycol (PEG). Transgenic seedlings grew significantly longer roots than wild-type ones did. Further enzymatic analysis showed an increased activity of superoxide dismutase (SOD) in transgenic seedlings. In addition, the level of malondialdehyde (MDA) was reduced in transgenics. qRT-PCR analysis showed altered expressions of several genes involved in the carotenoid biosynthesis in transgenic plants. These data results indicate that IbGGPS is involved in the biosynthesis of carotenoids in sweetpotato storage roots and likely associated with tolerance to osmotic stress. 相似文献
994.
995.
996.
997.
998.
Chandree?L. Beaulieu Jacek Majewski Jeremy Schwartzentruber Mark?E. Samuels Bridget?A. Fernandez Francois?P. Bernier Michael Brudno Bartha Knoppers Janet Marcadier David Dyment Shelin Adam Dennis?E. Bulman Steve?J.M. Jones Denise Avard Minh?Thu Nguyen Francois Rousseau Christian Marshall Richard?F. Wintle Yaoqing Shen Stephen?W. Scherer FORGE Canada Consortium Jan?M. Friedman Jacques?L. Michaud Kym?M. Boycott 《American journal of human genetics》2014,94(6):809-817
Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE’s impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally. 相似文献
999.
Clara?D. van?Karnebeek William?S. Sly Colin?J. Ross Ramona Salvarinova Joy Yaplito-Lee Saikat Santra Casper Shyr Gabriella?A. Horvath Patrice Eydoux Anna?M. Lehman Virginie Bernard Theresa Newlove Henry Ukpeh Anupam Chakrapani Mary?Anne Preece Sarah Ball James Pitt Hilary?D. Vallance Marion Coulter-Mackie Hien Nguyen Lin-Hua Zhang Amit?P. Bhavsar Graham Sinclair Abdul Waheed Wyeth?W. Wasserman Sylvia Stockler-Ipsiroglu 《American journal of human genetics》2014,94(3):453-461
Four children in three unrelated families (one consanguineous) presented with lethargy, hyperlactatemia, and hyperammonemia of unexplained origin during the neonatal period and early childhood. We identified and validated three different CA5A alterations, including a homozygous missense mutation (c.697T>C) in two siblings, a homozygous splice site mutation (c.555G>A) leading to skipping of exon 4, and a homozygous 4 kb deletion of exon 6. The deleterious nature of the homozygous mutation c.697T>C (p.Ser233Pro) was demonstrated by reduced enzymatic activity and increased temperature sensitivity. Carbonic anhydrase VA (CA-VA) was absent in liver in the child with the homozygous exon 6 deletion. The metabolite profiles in the affected individuals fit CA-VA deficiency, showing evidence of impaired provision of bicarbonate to the four enzymes that participate in key pathways in intermediary metabolism: carbamoylphosphate synthetase 1 (urea cycle), pyruvate carboxylase (anaplerosis, gluconeogenesis), propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase (branched chain amino acids catabolism). In the three children who were administered carglumic acid, hyperammonemia resolved. CA-VA deficiency should therefore be added to urea cycle defects, organic acidurias, and pyruvate carboxylase deficiency as a treatable condition in the differential diagnosis of hyperammonemia in the neonate and young child. 相似文献
1000.