全文获取类型
收费全文 | 2009篇 |
免费 | 95篇 |
出版年
2023年 | 10篇 |
2022年 | 19篇 |
2021年 | 56篇 |
2020年 | 28篇 |
2019年 | 37篇 |
2018年 | 50篇 |
2017年 | 41篇 |
2016年 | 41篇 |
2015年 | 70篇 |
2014年 | 101篇 |
2013年 | 149篇 |
2012年 | 181篇 |
2011年 | 171篇 |
2010年 | 116篇 |
2009年 | 94篇 |
2008年 | 106篇 |
2007年 | 99篇 |
2006年 | 77篇 |
2005年 | 94篇 |
2004年 | 95篇 |
2003年 | 57篇 |
2002年 | 62篇 |
2001年 | 23篇 |
2000年 | 20篇 |
1999年 | 27篇 |
1998年 | 10篇 |
1997年 | 10篇 |
1996年 | 12篇 |
1995年 | 7篇 |
1994年 | 13篇 |
1993年 | 4篇 |
1992年 | 17篇 |
1991年 | 15篇 |
1990年 | 13篇 |
1989年 | 20篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 10篇 |
1985年 | 10篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 10篇 |
1980年 | 9篇 |
1979年 | 11篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1975年 | 20篇 |
1974年 | 16篇 |
1970年 | 4篇 |
排序方式: 共有2104条查询结果,搜索用时 15 毫秒
941.
Rakesh Kumar Edward E. Knaus Leonard I. Wiebe 《Nucleosides, nucleotides & nucleic acids》2013,32(9):895-904
Abstract (E)-5-(2-lodovinyl)-2′-fluoro-3′-0-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2′-deoxyuridine (11) was synthesized for future evaluation as a lipophilic, brain-selective, pyrimidine phosphorylase-resistant, antiviral agent for the treatment of Herpes simplex encephalitis (HSE). Treatment of (E)-5-(2-iodovinyl)-2′-fluoro-2′-deoxyuridine (6) with TBDMSCI in the presence of imidazole in DMF yielded the protected 5′-O-t-butyldimethylsilyl derivative (7). Subsequent reaction with nicotinoyl chloride hydrochloride in pyridine afforded (E)-5-(-2-iodovinyl)-2′-fluoro-3′-O-(3-pyridylcarbonyl)-5′-O-t-butyldimethylsily-2′-deoxyuridine (8). Deprotection of the silyl ether moiety of 8 with n-Bu4N+F? and quaternization of the resulting 3′-O-(3-pyridylcarbonyl) derivative 9 using iodomethane afforded the corresponding 1-methylpyridinium salt 10. The latter was reduced with sodium dithionite to yield (E)-5-(2-iodovinyl)-2′-fluoro-3′-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2′-deoxyuridine (11). 相似文献
942.
Harpal Singh Sameer Dixit Praveen Chandra Verma Pradhyumna Kumar Singh 《Plant signaling & behavior》2013,8(9)
Peroxidases are the ubiquitous enzyme and reported to be present in all living genera. They catalyses reduction of peroxide and generate reactive oxygen species. In the present study we demonstrated that insect infestation induces peroxidase activity in sap and total soluble protein (TSP) of plant leaves. Three important crop plants viz. tomato, cowpea and cotton were used for this study. After infestation of chewing insect, Peroxidase activity in the sap and TSP of all the studied plants were enhanced in the range of 1.6 to 3.14 fold. Similar observations were also obtained with feeding of sap sucking insects, in which increment in peroxidase activity of sap and TSP was in the range of 1.8 to 2.53 fold. Enhanced peroxidase activity was reconfirmed by in-gel peroxidase assay. Enzyme kinetic study showed turn over efficiency of peroxidase from cotton (~101.3 min-1) was almost similar to tomato (~100.8 min-1) but higher than cowpea (~98.21min-1). MS/MS analysis of observed band showed significant similarity with the reported peroxidases in database. 相似文献
943.
Sameer Dixit Santosh Kumar Upadhyay Harpal Singh Bindu Pandey Krishnappa Chandrashekar Praveen Chandra Verma 《Plant signaling & behavior》2013,8(10)
Pectin methylesterases (PME; EC 3.1.1.11) involved in de-esterification of pectin and have applicability in food, textiles, wines, pulp, and paper industries. In the present study, we compared PME activity of different parts of 3 Datura species and found that fruit coat showed maximum PME activity followed by leaf and seed. PME from leaves of D. stramonium (DsPME) was purified and characterized. DsPME showed optimum activity at 60 °C and pH 9 in the presence of 0.3 M NaCl. DsPME was stable at 70 °C and retained more than 40% activity after 60 min of incubation. However, enzyme activity completely abolished at 80 after 5 min of incubation. It follows Michaelis-Menten enzyme kinetics. Km and Vmax with citrus pectin were 0.008 mg/ml and 16.96 µmol/min, respectively. DsPME in combination with polygalactourenase (PGA) increased the clarity of orange, apple, pomegranate and pineapple juices by 2.9, 2.6, 2.3, and 3.6 fold, respectively in comparison to PGA alone. Due to very high de-esterification activity, easy denaturation and significant efficacy in incrementing clarification of fruit juice makes DsPME useful for industrial application. 相似文献
944.
Sonali B. Rohamare Vaishali Dixit Pavan Kumar Nareddy D. Sivaramakrishna Musti J. Swamy Sushama M. Gaikwad 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(3):708-716
Polyproline II (PPII) fold, an unusual structural element was detected in the serine protease from Nocardiopsis sp. NCIM 5124 (NprotI) based on far UV circular dichroism spectrum, structural transitions of the enzyme in presence of GdnHCl and a distinct isodichroic point in chemical and thermal denaturation. The functional activity and conformational transitions of the enzyme were studied under various denaturing conditions. Enzymatic activity of NprotI was stable in the vicinity of GdnHCl upto 6.0 M concentration, organic solvents viz. methanol, ethanol, propanol (all 90% v/v), acetonitrile (75% v/v) and proteases such as trypsin, chymotrypsin and proteinase K (NprotI:protease 10:1). NprotI seems to be a kinetically stable protease with a high energy barrier between folded and unfolded states. Also, an enhancement in the activity of the enzyme was observed in 1 M GdnHCl upto 8 h, in organic solvents (75% v/v) for 72 h and in presence of proteolytic enzymes. The polyproline fold remained unaltered or became more prominent under the above mentioned conditions. However, it diminished gradually during thermal denaturation above 60 °C. Thermal transition studies by differential scanning calorimetry (DSC) showed scan rate dependence as well as irreversibility of denaturation, the properties characteristic of kinetically stable proteins. This is the first report of PPII helix being the global conformation of a non structural protein, an alkaline serine protease, from a microbial source, imparting kinetic stability to the protein. 相似文献
945.
Maria Tropeano Joo Wook Ahn Richard J. B. Dobson Gerome Breen James Rucker Abhishek Dixit Deb K. Pal Peter McGuffin Anne Farmer Peter S. White Joris Andrieux Evangelos Vassos Caroline Mackie Ogilvie Sarah Curran David A Collier 《PloS one》2013,8(4)
Copy number variants (CNVs) at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH); cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR = 2.59; p = 0.0005), and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR = 5.62; p = 0.0002), but not in females (OR = 1.19, p = 0.673). The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR = 2.59; p = 0.0005), located in the 0.83 Mb genomic region between 15.49–16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13.11 represent incompletely penetrant pathogenic mutations that predispose to a range of neurodevelopmental disorders, and suggest a sex-limited effect on the penetrance of the pathological phenotypes at the 16p13.11 locus. 相似文献
946.
Marina Genschaft Thomas Huebner Franziska Plessow Vasiliki N. Ikonomidou Nasreddin Abolmaali Franziska Krone Andre Hoffmann Elisabeth Holfeld Peter Vorwerk Christof Kramm Bernd Gruhn Elisabeth Koustenis Pablo Hernaiz-Driever Rakesh Mandal Meinolf Suttorp Thomas Hummel Chrysanthy Ikonomidou Clemens Kirschbaum Michael N. Smolka 《PloS one》2013,8(11)
Objective
Using multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing.Methods
We examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15–22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB’s integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed.Results
Mean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes.Interpretation
Findings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood. 相似文献947.
Alexandra Abramsson Petronella Kettunen Rakesh K. Banote Emelie Lott Mei Li Anders Arner Henrik Zetterberg 《Developmental biology》2013
The amyloid precursor protein (APP) is a transmembrane protein mostly recognized for its association with Alzheimer's disease. The physiological function of APP is still not completely understood much because of the redundancy between genes in the APP family. In this study we have used zebrafish to study the physiological function of the zebrafish APP homologue, appb, during development. We show that appb is expressed in post-mitotic neurons in the spinal cord. Knockdown of appb by 50–60% results in a behavioral phenotype with increased spontaneous coiling and prolonged touch-induced activity. The spinal cord motor neurons in these embryos show defective formation and axonal outgrowth patterning. Reduction in Appb also results in patterning defects and changed density of pre- and post-synapses in the neuromuscular junctions. Together, our data show that development of functional locomotion in zebrafish depends on a critical role of Appb in the patterning of motor neurons and neuromuscular junctions. 相似文献
948.
Rakesh Santhanam Xiaoying Rong Ying Huang Michael Goodfellow 《Antonie van Leeuwenhoek》2013,103(1):79-87
Two filamentous actinomycetes isolated from a hay meadow soil were provisionally assigned to the genus Streptomyces based on morphological features. The isolates were found to have chemical and morphological properties typical of the genus Streptomyces and formed distinct phyletic lines in the 16S rRNA gene tree. Isolate I36T was most closely related to Streptomyces glauciniger NBRC 100913T and isolate I37T to Streptomyces mirabilis NBRC 13450T. Low DNA:DNA relatedness values were recorded between each of the isolates and their closest phylogenetic neighbour. The isolates were also distinguished from their nearest phylogenetic neighbour, and from one another, using a combination of phenotypic properties. These data indicate that the isolates should be recognised as new species in the genus Streptomyces. The names proposed for these new taxa are Streptomyces erringtonii sp. nov. and Streptomyces kaempferi sp. nov. with isolate I36T (=CGMCC 4.7016T = KACC 15424T) and isolate I37T (=CGMCC 4.7020T = KACC 15428T) as the respective type strains. 相似文献
949.
Cyanobacteria are a rich source of vast array of bioactive molecules including toxins with wide pharmaceutical importance. They show varied bioactivities like antitumor, antiviral, antibacterial, antifungal, antimalarial, antimycotics, antiproliferative, cytotoxicity, immunosuppressive agents and multi-drug resistance reversers. A number of techniques are now developed and standardized for the extraction, isolation, detection and purification of cyanobacterial bioactive molecules. Some of the compounds are showing interesting results and have successfully reached to phase II and phase III of clinical trials. These compounds also serve as lead compounds for the development of synthetic analogues with improved bioactivity. Cyanobacterial bioactive molecules hold a bright and promising future in scientific research and great opportunity for drug discovery. This review mainly focuses on anticancerous, antiviral and antibacterial compounds from cyanobacteria; their clinical status; extraction and detection techniques. 相似文献
950.