全文获取类型
收费全文 | 2397篇 |
免费 | 210篇 |
国内免费 | 1篇 |
专业分类
2608篇 |
出版年
2023年 | 12篇 |
2022年 | 31篇 |
2021年 | 70篇 |
2020年 | 28篇 |
2019年 | 56篇 |
2018年 | 51篇 |
2017年 | 45篇 |
2016年 | 70篇 |
2015年 | 115篇 |
2014年 | 124篇 |
2013年 | 192篇 |
2012年 | 215篇 |
2011年 | 211篇 |
2010年 | 145篇 |
2009年 | 99篇 |
2008年 | 152篇 |
2007年 | 140篇 |
2006年 | 133篇 |
2005年 | 127篇 |
2004年 | 116篇 |
2003年 | 105篇 |
2002年 | 97篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 18篇 |
1998年 | 13篇 |
1997年 | 10篇 |
1996年 | 13篇 |
1995年 | 16篇 |
1994年 | 9篇 |
1993年 | 20篇 |
1990年 | 4篇 |
1988年 | 3篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 11篇 |
1984年 | 6篇 |
1983年 | 12篇 |
1982年 | 11篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 9篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1971年 | 5篇 |
1966年 | 3篇 |
1965年 | 5篇 |
排序方式: 共有2608条查询结果,搜索用时 15 毫秒
81.
Sara Karami Paul Brennan Philip S. Rosenberg Marie Navratilova Dana Mates David Zaridze Vladimir Janout Helena Kollarova Vladimir Bencko Vsevolod Matveev Neonila Szeszenia-Dabrowska Ivana Holcatova Meredith Yeager Stephen Chanock Idan Menashe Nathaniel Rothman Wong-Ho Chow Paolo Boffetta Lee E. Moore 《PloS one》2009,4(9)
In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR), most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology. RCC cases (N = 777) and controls (N = 1,035) were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P) tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP) sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02) and retinoid-X-receptor-alpha (RXRA) (p-value = 0.10) were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991) across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09–1.57) haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3′ of the coding sequence (rs748964, rs3118523), increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings. 相似文献
82.
Morphine and Cocaine Exert Common Chronic Actions on Tyrosine Hydroxylase in Dopaminergic Brain Reward Regions 总被引:9,自引:0,他引:9
We studied levels of tyrosine hydroxylase immunoreactivity and phosphorylation state in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in an effort to understand better the mechanisms by which these brain reward regions are influenced by opiates and cocaine. In the VTA, chronic, but not acute, administration of either morphine or cocaine increased levels of tyrosine hydroxylase immunoreactivity by 30-40%, with no change observed in the relative phosphorylation state of the enzyme. In the NAc, chronic, but not acute, morphine and cocaine treatments decreased the phosphorylation state of tyrosine hydroxylase, without a change in its total amount. In contrast, morphine and cocaine did not regulate tyrosine hydroxylase in the substantia nigra or caudate/putamen, brain regions generally not implicated in drug reward. Morphine and cocaine regulation of tyrosine hydroxylase could represent part of a common biochemical basis of morphine and cocaine addiction and craving. 相似文献
83.
Introduction
Fibromyalgia is difficult to treat and requires the use of multiple approaches. This study is a randomized controlled trial of qigong compared with a wait-list control group in fibromyalgia.Methods
One hundred participants were randomly assigned to immediate or delayed practice groups, with the delayed group receiving training at the end of the control period. Qigong training (level 1 Chaoyi Fanhuan Qigong, CFQ), given over three half-days, was followed by weekly review/practice sessions for eight weeks; participants were also asked to practice at home for 45 to 60 minutes per day for this interval. Outcomes were pain, impact, sleep, physical function and mental function, and these were recorded at baseline, eight weeks, four months and six months. Immediate and delayed practice groups were analyzed individually compared to the control group, and as a combination group.Results
In both the immediate and delayed treatment groups, CFQ demonstrated significant improvements in pain, impact, sleep, physical function and mental function when compared to the wait-list/usual care control group at eight weeks, with benefits extending beyond this time. Analysis of combined data indicated significant changes for all measures at all times for six months, with only one exception. Post-hoc analysis based on self-reported practice times indicated greater benefit with the per protocol group compared to minimal practice.Conclusions
This study demonstrates that CFQ, a particular form of qigong, provides long-term benefits in several core domains in fibromyalgia. CFQ may be a useful adjuvant self-care treatment for fibromyalgia.Trial registration
clinicaltrials.gov NCT00938834. 相似文献84.
85.
Mark R. Herbert Dana L. Siegel Lena Staszewski Charmagne Cayanan Urmi Banerjee Sangeeta Dhamija Jennifer Anderson Amy Fan Li Wang Peter Rix Andrew K. Shiau Tadimeti S. Rao Stewart A. Noble Richard A. Heyman Eric Bischoff Mausumee Guha Ayman Kabakibi Anthony B. Pinkerton 《Bioorganic & medicinal chemistry letters》2010,20(19):5718-5721
Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist 32, which was shown to have activity in a rodent model for diabetes. 相似文献
86.
Adam R. Boyko Pascale Quignon Lin Li Jeffrey J. Schoenebeck Jeremiah D. Degenhardt Kirk E. Lohmueller Keyan Zhao Abra Brisbin Heidi G. Parker Bridgett M. vonHoldt Michele Cargill Adam Auton Andy Reynolds Abdel G. Elkahloun Marta Castelhano Dana S. Mosher Nathan B. Sutter Gary S. Johnson John Novembre Melissa J. Hubisz Adam Siepel Robert K. Wayne Carlos D. Bustamante Elaine A. Ostrander 《PLoS biology》2010,8(8)
Domestic dogs exhibit tremendous phenotypic diversity, including a greater
variation in body size than any other terrestrial mammal. Here, we generate a
high density map of canine genetic variation by genotyping 915 dogs from 80
domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across
60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource
with external measurements from breed standards and individuals as well as
skeletal measurements from museum specimens, we identify 51 regions of the dog
genome associated with phenotypic variation among breeds in 57 traits. The
complex traits include average breed body size and external body dimensions and
cranial, dental, and long bone shape and size with and without allometric
scaling. In contrast to the results from association mapping of quantitative
traits in humans and domesticated plants, we find that across dog breeds, a
small number of quantitative trait loci (≤3) explain the majority of
phenotypic variation for most of the traits we studied. In addition, many
genomic regions show signatures of recent selection, with most of the highly
differentiated regions being associated with breed-defining traits such as body
size, coat characteristics, and ear floppiness. Our results demonstrate the
efficacy of mapping multiple traits in the domestic dog using a database of
genotyped individuals and highlight the important role human-directed selection
has played in altering the genetic architecture of key traits in this important
species. 相似文献
87.
Marko Simunovic Angela Coates Charles H. Goldsmith Lehana Thabane Dana Reeson Andrew Smith Robin S. McLeod Franco DeNardi Timothy J. Whelan Mark N. Levine 《CMAJ》2010,182(12):1301-1306
Background
Following surgery for rectal cancer, two unfortunate outcomes for patients are permanent colostomy and local recurrence of cancer. We tested whether a quality-improvement strategy to change surgical practice would improve these outcomes.Methods
Sixteen hospitals were cluster-randomized to the intervention (Quality Initiative in Rectal Cancer strategy) or control (normal practice) arm. Consecutive patients with primary rectal cancer were accrued from May 2002 to December 2004. Surgeons at hospitals in the intervention arm could voluntarily participate by attending workshops, using opinion leaders, inviting a study team surgeon to demonstrate optimal techniques of total mesorectal excision, completing postoperative questionnaires, and receiving audits and feedback. Main outcome measures were hospital rates of permanent colostomy and local recurrence of cancer.Results
A total of 56 surgeons (n = 558 patients) participated in the intervention arm and 49 surgeons (n = 457 patients) in the control arm. The median follow-up of patients was 3.6 years. In the intervention arm, 70% of surgeons participated in workshops, 70% in intraoperative demonstrations and 71% in postoperative questionnaires. Surgeons who had an intraoperative demonstration provided care to 86% of the patients in the intervention arm. The rates of permanent colostomy were 39% in the intervention arm and 41% in the control arm (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.63–1.48). The rates of local recurrence were 7% in the intervention arm and 6% in the control arm (OR 1.06, 95% CI 0.68–1.64).Interpretation
Despite good participation by surgeons, the resource-intense quality-improvement strategy did not reduce hospital rates of permanent colostomy or local recurrence compared with usual practice. (ClinicalTrials.gov trial register no. .)Following surgery for rectal cancer, two unfortunate outcomes for patients are permanent colostomy and local recurrence of the cancer. Local recurrence is especially feared, because it is usually inoperable and patients can suffer a slow, painful death. NCT001821301 The use of total mesorectal excision, which involves dissection of the lymph node-bearing portion of the rectum,2 has resulted in improved outcomes, with local recurrence rates as low as 1%–5% and rates of permanent colostomy of 10%–15%.3–6 Population-based rates of local recurrence are unavailable for any North American jurisdiction, although a Canadian hospital series found that rates varied from 10% to 45% based on the practice volume and training of surgeons.7 A surgical report on health regions in the province of Ontario (population 13 million) found that rates of permanent colostomy varied from 31% to 41%.8 This geographic variation in outcomes, together with rates of inferior outcomes as compared to outcomes specific to total mesorectal excision, suggest that gaps exist in the quality of rectal surgery provided to patients with rectal cancer.Quality-improvement strategies for encouraging physicians to change practice include continuing medical education, the use of opinion leaders, and audit and feedback.9–11 As well, improvement may be enhanced by using a participatory and supportive approach that focuses on the system and not on individual practitioners.12,13 The small number of studies that have evaluated changes in surgeons’ practices often have targeted process measures, such as preoperative ordering of antibiotics, rather than patient outcomes, such as recurrence of cancer.14,15We tested whether use of a surgeon-directed quality-improvement strategy would improve hospital rates of permanent colostomy and local recurrence of cancer among patients undergoing surgery for rectal cancer. We used the Quality Initiative in Rectal Cancer (QIRC) strategy, which integrates quality-improvement interventions and principles to encourage surgeons to provide optimal total mesorectal excision to patients with rectal cancer.16 相似文献88.
Udom Chaithong Wej Choochote Kittichai Kamsuk Atchariya Jitpakdi Pongsri Tippawangkosol Dana Chaiyasit Daruna Champakaew Benjawan Tuetun Benjawan Pitasawat 《Journal of vector ecology》2006,31(1):138-144
Ethanolic extracts derived from three species of the Piperaceae (pepper) family, Piper longum L., P. ribesoides Wall., and P. sarmentosum Roxb. ex Hunt., were evaluated for efficacy against early 4th instar larvae of Aedes aegypti mosquitoes using larvicidal bioassays. The highest larvicidal efficacy was established from P. longum, followed by P. sarmentosum and P. ribesoides, with LC50 values of 2.23, 4.06, and 8.13 ppm, respectively. Observations of morphological alterations on treated 4th instar larvae revealed that most organs, except anal papillae, had a normal structural appearance that was similar to controls. Under light microscopy, the internal structures of anal papillae in the treated larvae showed shrinkage, while the external features were normal in appearance. Ultrastructural studies, however, clearly demonstrated external destruction, with extensive damage and shrunken cuticle of the anal papillae. The structural deformation of anal papillae probably led to their dysfunction, which may be intrinsically associated with the death of the larvae. This study affords some evidence regarding the action site of the pepper extracts and suggests their potential in developing new types of larvicides used for mosquito control. 相似文献
89.
90.
Kristopher P. Croome David D. Lee Justin M. Burns Dana K. Perry Andrew P. Keaveny C. Burcin Taner 《PloS one》2015,10(10)