全文获取类型
收费全文 | 1197篇 |
免费 | 82篇 |
出版年
2023年 | 12篇 |
2022年 | 13篇 |
2021年 | 38篇 |
2020年 | 25篇 |
2019年 | 17篇 |
2018年 | 33篇 |
2017年 | 20篇 |
2016年 | 36篇 |
2015年 | 52篇 |
2014年 | 59篇 |
2013年 | 80篇 |
2012年 | 112篇 |
2011年 | 92篇 |
2010年 | 57篇 |
2009年 | 46篇 |
2008年 | 70篇 |
2007年 | 46篇 |
2006年 | 37篇 |
2005年 | 44篇 |
2004年 | 33篇 |
2003年 | 35篇 |
2002年 | 20篇 |
2001年 | 32篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 5篇 |
1997年 | 7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 |
1969年 | 3篇 |
排序方式: 共有1279条查询结果,搜索用时 15 毫秒
41.
Ambastha Vivek Chauhan Garima Tiwari Budhi Sagar Tripathy Baishnab C 《Protoplasma》2020,257(3):841-851
Protoplasma - Absorption of excess excitation energy induces overproduction of singlet oxygen (1O2) in plants. The major sources of singlet oxygen production are chlorophyll and its intermediates... 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.
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
45.
46.
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47.
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
48.
Epigenetic mechanisms of plant stress responses and adaptation 总被引:3,自引:0,他引:3
Pranav Pankaj Sahu Garima Pandey Namisha Sharma Swati Puranik Mehanathan Muthamilarasan Manoj Prasad 《Plant cell reports》2013,32(8):1151-1159
Epigenetics has become one of the hottest topics of research in plant functional genomics since it appears promising in deciphering and imparting stress-adaptive potential in crops and other plant species. Recently, numerous studies have provided new insights into the epigenetic control of stress adaptation. Epigenetic control of stress-induced phenotypic response of plants involves gene regulation. Growing evidence suggest that methylation of DNA in response to stress leads to the variation in phenotype. Transposon mobility, siRNA-mediated methylation and host methyltransferase activation have been implicated in this process. This review presents the current status of epigenetics of plant stress responses with a view to use this knowledge towards engineering plants for stress tolerance. 相似文献
49.
How DNA Polymerase X Preferentially Accommodates Incoming dATP Opposite 8-Oxoguanine on the Template
Benedetta Sampoli Benítez Zachary R. Barbati Karunesh Arora Jasmina Bogdanovic Tamar Schlick 《Biophysical journal》2013
The modified base 8-oxo-7,8-dihydro-2′-deoxyguanosine (oxoG) is a common DNA adduct produced by the oxidation of DNA by reactive oxygen species. Kinetic data reveal that DNA polymerase X (pol X) from the African swine fever virus incorporates adenine (dATP) opposite to oxoG with higher efficiency than the non-damaged G:C basepair. To help interpret the kinetic data, we perform molecular dynamics simulations of pol X/DNA complexes, in which the template base opposite to the incoming dNTP (dCTP, dATP, dGTP) is oxoG. Our results suggest that pol X accommodates the oxoGsyn:A mispair by sampling closed active conformations that mirror those observed in traditional Watson-Crick complexes. Moreover, for both the oxoGsyn:A and oxoG:C ternary complexes, conformational sampling of the polymerase follows previously described large subdomain movements, local residue motions, and active site reorganization. Interestingly, the oxoGsyn:A system exhibits superior active site geometry in comparison to the oxoG:C system. Simulations for the other mismatch basepair complexes reveal large protein subdomain movement for all systems, except for oxoG:G, which samples conformations close to the open state. In addition, active site geometry and basepairing of the template base with the incoming nucleotide, reveal distortions and misalignments that range from moderate (i.e., oxoG:Asyn) to extreme (i.e., oxoGanti/syn:G). These results agree with the available kinetic data for pol X and provide structural insights regarding the mechanism by which this polymerase can accommodate incoming nucleotides opposite oxoG. Our simulations also support the notion that α-helix E is involved both in DNA binding and active site stabilization. Our proposed mechanism by which pol X can preferentially accommodate dATP opposite template oxoG further underscores the role that enzyme dynamics and conformational sampling operate in polymerase fidelity and function. 相似文献
50.
Gunjan Arora Andaleeb Sajid Mary Diana Arulanandh Richa Misra Anshika Singhal Santosh Kumar Lalit K. Singh Abid R. Mattoo Rishi Raj Souvik Maiti Sharmila Basu-Modak Yogendra Singh 《Biometals》2013,26(5):715-730
Bacillus anthracis Ser/Thr protein kinase PrkC (BasPrkC) is important for virulence of the bacterium within the host. Homologs of PrkC and its cognate phosphatase PrpC (BasPrpC) are the most conserved mediators of signaling events in diverse bacteria. BasPrkC homolog in Bacillus subtilis regulates critical processes like spore germination and BasPrpC modulates the activity of BasPrkC by dephosphorylation. So far, biochemical and genetic studies have provided important insights into the roles of BasPrkC and BasPrpC; however, regulation of their activities is not known. We studied the regulation of BasPrkC/BasPrpC pair and observed that Zn2+ metal ions can alter their activities. Zn2+ promotes BasPrkC kinase activity while inhibits the BasPrpC phosphatase activity. Concentration of Zn2+ in growing B. anthracis cells was found to vary with growth phase. Zn2+ was found to be lowest in log phase cells while it was highest in spores. This variation in Zn2+ concentration is significant for understanding the antagonistic activities of BasPrkC/BasPrpC pair. Our results also show that BasPrkC activity is modulated by temperature changes and kinase inhibitors. Additionally, we identified Elongation Factor Tu (BasEf-Tu) as a substrate of BasPrkC/BasPrpC pair and assessed the impact of their regulation on BasEf-Tu phosphorylation. Based on these results, we propose Zn2+ as an important regulator of BasPrkC/BasPrpC mediated phosphorylation cascades. Thus, this study reveals additional means by which BasPrkC can be activated leading to autophosphorylation and substrate phosphorylation. 相似文献