全文获取类型
收费全文 | 1282篇 |
免费 | 81篇 |
国内免费 | 1篇 |
出版年
2023年 | 9篇 |
2022年 | 23篇 |
2021年 | 48篇 |
2020年 | 28篇 |
2019年 | 21篇 |
2018年 | 37篇 |
2017年 | 24篇 |
2016年 | 41篇 |
2015年 | 55篇 |
2014年 | 71篇 |
2013年 | 87篇 |
2012年 | 120篇 |
2011年 | 104篇 |
2010年 | 54篇 |
2009年 | 37篇 |
2008年 | 72篇 |
2007年 | 46篇 |
2006年 | 40篇 |
2005年 | 50篇 |
2004年 | 33篇 |
2003年 | 40篇 |
2002年 | 19篇 |
2001年 | 32篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 6篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 13篇 |
1991年 | 12篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 13篇 |
1978年 | 4篇 |
1973年 | 13篇 |
1972年 | 11篇 |
1971年 | 9篇 |
1970年 | 6篇 |
1966年 | 3篇 |
排序方式: 共有1364条查询结果,搜索用时 15 毫秒
41.
Emmanuel S. Buys Yu-Chieh Ko Clemens Alt Sarah R. Hayton Alexander Jones Laurel T. Tainsh Ruiyi Ren Andrea Giani Maeva Clerté Emma Abernathy Robert E. T. Tainsh Dong-Jin Oh Rajeev Malhotra Pankaj Arora Nadine de Waard Binglan Yu Raphael Turcotte Daniel Nathan Marielle Scherrer-Crosbie Stephanie J. Loomis Jae H. Kang Charles P. Lin Haiyan Gong Douglas J. Rhee Peter Brouckaert Janey L. Wiggs Meredith S. Gregory Louis R. Pasquale Kenneth D. Bloch Bruce R. Ksander 《PloS one》2013,8(3)
Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG. 相似文献
42.
Arora Sakshi Singh Amarjeet Kumar Chaudhary Bhupendra 《Plant Cell, Tissue and Organ Culture》2020,141(3):511-531
Plant Cell, Tissue and Organ Culture (PCTOC) - In vitro regeneration of cotton seems to be highly genotype dependent and typically ensues through the extraordinarily complex mechanism of somatic... 相似文献
43.
44.
Wareed Ahmed Anuradha Gopal Bhat Majety Naga Leelaram Shruti Menon Valakunja Nagaraja 《Nucleic acids research》2013,41(15):7462-7471
Bacterial DNA topoisomerase I (topoI) carries out relaxation of negatively supercoiled DNA through a series of orchestrated steps, DNA binding, cleavage, strand passage and religation. The N-terminal domain (NTD) of the type IA topoisomerases harbor DNA cleavage and religation activities, but the carboxyl terminal domain (CTD) is highly diverse. Most of these enzymes contain a varied number of Zn2+ finger motifs in the CTD. The Zn2+ finger motifs were found to be essential in Escherichia coli topoI but dispensable in the Thermotoga maritima enzyme. Although, the CTD of mycobacterial topoI lacks Zn2+ fingers, it is indispensable for the DNA relaxation activity of the enzyme. The divergent CTD harbors three stretches of basic amino acids needed for the strand passage step of the reaction as demonstrated by a new assay. We also show that the basic amino acids constitute an independent DNA-binding site apart from the NTD and assist the simultaneous binding of two molecules of DNA to the enzyme, as required during the catalytic step. Although the NTD binds to DNA in a site-specific fashion to carry out DNA cleavage and religation, the basic residues in CTD bind to non-scissile DNA in a sequence-independent manner to promote the crucial strand passage step during DNA relaxation. The loss of Zn2+ fingers from the mycobacterial topoI could be associated with Zn2+ export and homeostasis. 相似文献
45.
Assessment of systematic effects of methodological characteristics on candidate genetic associations
Badr Aljasir John P. A. Ioannidis Alex Yurkiewich David Moher Julian P. T. Higgins Paul Arora Julian Little 《Human genetics》2013,132(2):167-178
Candidate genetic association studies have been found to have a low replication rate in the past. Here, we aimed to assess whether aspects of reported methodological characteristics in genetic association studies may be related to the magnitude of effects observed. An observational, literature-based investigation of 511 case–control studies of genetic association studies indexed in 2007, was undertaken. Meta-regression analyses were used to assess the relationship between 23 reported methodological characteristics and the magnitude of genetic associations. The 511 studies had been conducted in 52 countries and were published in 220 journals (median impact factor 5.1). The multivariate meta-regression model of methodological characteristics plus disease category accounted for 17.2 % of the between-study variance in the magnitude of the reported genetic associations. Our findings are consistent with the view that better conducted and better reported genetic association research may lead to less inflated results. 相似文献
46.
Mayank Singh Clayton R. Hunt Raj K. Pandita Rakesh Kumar Chin-Rang Yang Nobuo Horikoshi Robert Bachoo Sara Serag Michael D. Story Jerry W. Shay Simon N. Powell Arun Gupta Jessie Jeffery Shruti Pandita Benjamin P. C. Chen Dorothee Deckbar Markus L?brich Qin Yang Kum Kum Khanna Howard J. Worman Tej K. Pandita 《Molecular and cellular biology》2013,33(16):3390
47.
48.
Paul Arora Priya Vasa Darren Brenner Karl Iglar Phil McFarlane Howard Morrison Alaa Badawi 《CMAJ》2013,185(9):E417-E423
Background:
Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults.Methods:
We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status.Results:
The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m2 or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%).Interpretation:
The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease.Chronic kidney disease is defined as the presence of kidney damage or reduced kidney function for more than 3 months and requires either a measured or estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m2, or the presence of abnormalities in urine sediment, renal imaging or biopsy results.1 Between 1.3 million and 2.9 million Canadians are estimated to have chronic kidney disease, based on an extrapolation of the prevalence of end-stage renal disease.2 In the United States, the 1999–2004 National Health and Nutrition Examination Survey reported a prevalence of 5.0% for stage 1 and 2 disease and 8.1% for stage 3 and 4 disease.3,4Chronic kidney disease has been identified as a risk factor for death and cardiovascular-related morbidity and is a substantial burden on the health care system.1,5 Hemodialysis costs the Canadian health care system about $60 000 per patient per year of treatment.1 The increasing prevalence of chronic kidney disease can be attributed in part to the growing elderly population and to increasing rates of diabetes and hypertension.1,6,7Albuminuria, which can result from abnormal vascular permeability, atherosclerosis or renal disease, has gained recognition as an independent risk factor for progressive renal dysfunction and adverse cardiovascular outcomes.8–10 In earlier stages of chronic kidney disease, albuminuria has been shown to be more predictive of renal and cardiovascular events than eGFR.4,9 This has prompted the call for a new risk stratification for cardiovascular outcomes based on both eGFR and albuminuria.11A recent review advocated screening people for chronic kidney disease if they have hypertension, diabetes, clinically evident cardiovascular disease or a family history of kidney failure or are more than 60 years old.4 The Canadian Society of Nephrology published guidelines on the management of chronic kidney disease but did not offer guidance on screening.1 The Canadian Diabetes Association recommends annual screening with the use of an albumin:creatinine ratio,12 and the Canadian Hypertension Education Program guideline recommends urinalysis as part of the initial assessment of hypertension.13 Screening for chronic kidney disease on the basis of eGFR and albuminuria is not considered to be cost-effective in the general population, among older people or among people with hypertension.14The objective of our study was to use direct measures (biomarkers) of kidney function to generate nationally representative, population-based prevalence estimates of chronic kidney disease among Canadian adults overall and in clinically relevant groups. 相似文献49.
Gita Subba Rao Sneh Arora Sarika Kataria 《Journal of biomolecular structure & dynamics》2013,31(6):1053-1058
Abstract Enzymes of the subtilisin family, of which proteinase K is a member, have been studied extensively on account of their numerous biological applications. Specific inhibitors of the proteinases are of immense importance in regulating their activity so as to protect the cells against uncontrolled proteolysis. Using the specific design principles of peptides containing dehydro-Alanine (ΔAla), generated by our theoretical calculations, we present here the design of an inhibitor of proteinase K. Energy minimization and molecular modeling of the interaction of the designed tetrapeptide with the recognition site of proteinase K indicate that it is an effective inhibitor. 相似文献
50.