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1.
2.
An asymptomatic carrier and all six of his family members were detected positive for HBV DNA in their peripheral blood leukocytes (PBL), by polymerase chain reaction. Direct sequencing of the amplified DNA revealed that the HBV DNA from the carrier and his wife was of subtype ayw. Interestingly, the amplified HBV DNA from the five other members of the family was found to be not only of subtype adw but also contained G to A mutation at nucleotide position 587. This indicates the presence of established vaccine escape mutant of the virus (G145R) and suggests two different sources of infection within the family. Southern blot hybridization of EcoR1 digested DNA from PBL indicated presence of HBV DNA, integrated into cellular DNA and also in the form of free viral DNA. The study not only establishes the persistence of surface mutant G145R HBV DNA, within the PBL of HBsAg negative individuals from the non-vaccinated random population, but also suggests possible horizontal transmission of the mutant among the family members although none of the family members has received immunoprophylaxis against HBV or had clinically apparent disease or any other known risk factors of HBV infection. As all of them were seronegative for HBsAg/antiHBc, the presence of G145R mutant in the PBL signaled possibility of spread of the vaccine escape mutant virus by blood transfusion, unsafe injection practices or through sexual root. 相似文献
3.
Particulate matter less than PM10 and aromatic chemicals formed during incomplete combustion of organic matter are major environmental pollutants because of
their toxic potential. The present study reports on the respiratory morbidity pattern of people exposed to auto exhaust as
a result of the traffic load consisting of three varieties of vehicles (heavy, medium, and light) at three different points:
North (B), South (E), and Central (C) regions of Kolkata, India. Particle size distribution was analyzed by an Anderson cascade
impactor and volatile organic compounds (VOCs) were analyzed by sorbent tube and capillary gas chromatography with flame ionization
detector. Levels of VOCs, particularly benzene and toluene (at B, 15.2 and 20.1 μg/m3; at E, 67.4 and 74.6 μg/m3, and at C, 40.7 and 61.3 μg/m3, respectively), were found to be appreciably high in three sites in Kolkata compared with the values reported by the U.S.
EPA. PM10 concentrations also have been found to be higher than the Central Pollution Control Board of India’s permissible standard
(≤10 μm: B, 535.9; E, 909.2; C, 1114.5 μg/m3; <10–3.3 μm: B, 269.8 μg/m3; E, 460.1; C, 679.2 μg/m3; and <3.3–0.4 μm: B, 266.1; E, 449.1; C, 435.3 μg/m3). Pulmonary function tests (PFT) of 505 inhabitants were performed in the three different areas using Spirovit SP-10 and
Wrights peak flowmeter. The traffic load in the vicinity supported the occurrence of higher respiratory functional deterioration.
PFT status showed restrictive (3.76%), obstructive (3.17%), and combined restrictive and obstructive types (1.98%) of impairment.
Higher restrictive impairments in males might be due to their combined occupational and environmental exposures. The rate
of increase of the number of vehicles on the roads of the city adds to the risk of greater problems due to exposure to hazardous
substances that are less than PM10, in particular, polycyclic aromatic hydrocarbons and VOCs.
An erratum to this article can be found at 相似文献
4.
Evaluation of Hybridization Capture Versus Amplicon‐Based Methods for Whole‐Exome Sequencing 下载免费PDF全文
Eric Samorodnitsky Benjamin M. Jewell Raffi Hagopian Jharna Miya Michele R. Wing Ezra Lyon Senthilkumar Damodaran Darshna Bhatt Julie W. Reeser Jharna Datta Sameek Roychowdhury 《Human mutation》2015,36(9):903-914
Next‐generation sequencing has aided characterization of genomic variation. While whole‐genome sequencing may capture all possible mutations, whole‐exome sequencing remains cost‐effective and captures most phenotype‐altering mutations. Initial strategies for exome enrichment utilized a hybridization‐based capture approach. Recently, amplicon‐based methods were designed to simplify preparation and utilize smaller DNA inputs. We evaluated two hybridization capture‐based and two amplicon‐based whole‐exome sequencing approaches, utilizing both Illumina and Ion Torrent sequencers, comparing on‐target alignment, uniformity, and variant calling. While the amplicon methods had higher on‐target rates, the hybridization capture‐based approaches demonstrated better uniformity. All methods identified many of the same single‐nucleotide variants, but each amplicon‐based method missed variants detected by the other three methods and reported additional variants discordant with all three other technologies. Many of these potential false positives or negatives appear to result from limited coverage, low variant frequency, vicinity to read starts/ends, or the need for platform‐specific variant calling algorithms. All methods demonstrated effective copy‐number variant calling when evaluated against a single‐nucleotide polymorphism array. This study illustrates some differences between whole‐exome sequencing approaches, highlights the need for selecting appropriate variant calling based on capture method, and will aid laboratories in selecting their preferred approach. 相似文献
5.
Melanie A. Krook Julie W. Reeser Gabrielle Ernst Hannah Barker Max Wilberding Gary Li Hui-Zi Chen Sameek Roychowdhury 《British journal of cancer》2021,124(5):880
Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer 相似文献
6.
Sanjoy Roychowdhury Albert E Cram Al Aly Craig K Svensson 《Drug metabolism and disposition》2007,35(9):1463-1465
Bioactivation of parent drug to reactive metabolite(s) followed by protein haptenation has been suggested to be a critical step in the elicitation of cutaneous drug reactions. Although liver is believed to be the primary organ of drug bioactivation quantitatively, other organs including skin may also metabolize drugs. Cultured human epidermal keratinocytes and dermal fibroblasts have been shown to be capable of bioactivating sulfonamides and sulfones, giving rise to haptenated proteins. It is, however, unclear whether metabolic events in these isolated cells reflect bioactivation in vivo. Hence, split-thickness human skin explants were exposed to dapsone (DDS) or its arylhydroxylamine metabolite (dapsone hydroxylamine, D-NOH) and probed for protein haptenation. DDS and D-NOH were applied either epicutaneously or mixed in the medium (to mimic its entry into skin from the systemic circulation). DDS-protein adducts were readily detected in skin explants exposed to either DDS or D-NOH. Adducts were detected mainly in the upper epidermal region in response to epicutaneous application, whereas adducts were formed all over the explants when DDS/D-NOH were mixed in the culture medium. In addition, adducts were visible in HLA-DR+ cells, indicating their presence in the dendritic cell population in the skin. Our results demonstrate the ability of intact human skin to bioactivate DDS leading to protein haptenation. 相似文献
7.
Intake of arsenic from water, food composites and excretion through urine, hair from a studied population in West Bengal, India. 总被引:4,自引:0,他引:4
To evaluate the main intake source of arsenic by the villagers from arsenic-affected families in Jalangi and Domkol blocks in Mushidabad district, West Bengal-India, we determined the concentrations of arsenic in tube-well water and in food composites, mainly including vegetables and cereals collected from the surveyed families which were cultivated in that region. The daily dietary intakes of arsenic by the villagers were estimated and the excretions of arsenic through urine and hair were determined. The arsenic concentrations in hair and urine of the studied population living in mild (2.78 microg/L), moderate (30.7 microg/L) and high (118 microg/L) arsenic-affected families were 133, 1,391 and 4,713 microg/kg and 43.1, 244 and 336 microg/L, respectively. The linear regressions show good correlations between arsenic concentrations in water vs hair (r(2)=0.928, p<0.001) and water vs urine (r(2)=0.464, p<0.01). Approximately 29.4%, 58.1% and 62.1% of adult population from mild, moderate and high arsenic-affected families were suffering from arsenical skin manifestations. The mean arsenic concentrations of food composites (vegetables and cereals) in high arsenic-affected families are not significantly different from mild arsenic-affected families. The daily dietary intakes of arsenic from water and food composites of the studied population, living in high, moderate and mild arsenic-affected families were 568, 228 and 137 microg, respectively. The linear regressions show good correlations between arsenic concentrations in hair vs daily dietary intake (r(2)=0.452, p<0.001) and urine vs daily dietary intake (r(2)=0.134, p<0.001). The water for drinking contributed 6.07%, 26.7% and 58.1% of total arsenic in our study from mild, moderate and high arsenic-affected families. The result suggested that the contaminated water from high arsenic-affected families should be the main source for intake of arsenic. On contrary, the contribution of arsenic-contaminated food composites from mild and moderate arsenic-affected families might be the main source for intake of arsenic. The Food and Agriculture Organization/World Health Organization (FAO/WHO) provisional tolerable weekly intake (PTWI) values of arsenic in our study were 3.32, 5.75 and 12.9 microg/kg body weight/day from mild, moderate and high arsenic-affected families, respectively, which is higher than the recommended PTWI value of arsenic (2.1 microg/kg body weight/day). 相似文献
8.
Sanjoy Roychowdhury Piyush M Vyas Craig K Svensson 《Drug metabolism and disposition》2007,35(4):676-681
Bioactivation of sulfonamides and the subsequent formation of haptenated proteins is believed to be a critical step in the development of hypersensitivity reactions to these drugs. Numerous lines of evidence suggest that the presence of such adducts in dendritic cells (DCs) migrating to draining lymph nodes is essential for the development of cutaneous reactions to xenobiotics. Our objective was to determine the ability of human DCs to form drug-protein covalent adducts when exposed to sulfamethoxazole (SMX), dapsone (DDS), or their arylhydroxylamine metabolites [sulfamethoxazole hydroxylamine (S-NOH) and dapsone hydroxylamine (D-NOH)] and to take up preformed adduct. Naive and immature CD34+ KG-1 cells were incubated with SMX, DDS, or metabolites. Formation of haptenated proteins was probed using confocal microscopy and ELISA. Cells were also incubated with preformed adduct (drug-bovine serum albumin conjugate), and uptake was determined using confocal microscopy. Both naive and immature KG-1 cells were able to bioactivate DDS, forming drug-protein adducts, whereas cells showed very little protein haptenation when exposed to SMX. Exposure to S-NOH or D-NOH resulted in protein haptenation in both cell types. Both immature and naive KG-1 cells were able to take up preformed haptenated proteins. Thus, DCs may acquire haptenated proteins associated with drugs via intracellular bioactivation, uptake of reactive metabolites, or uptake of adduct formed and released by adjacent cells (e.g., keratinocytes). 相似文献
9.
Is methotrexate effective in ankylosing spondylitis? 总被引:5,自引:0,他引:5
Roychowdhury B Bintley-Bagot S Bulgen DY Thompson RN Tunn EJ Moots RJ 《Rheumatology (Oxford, England)》2002,41(11):1330-1332
10.
Roychowdhury S Loevner LA Yousem DM Chalian A Montone KT 《AJNR. American journal of neuroradiology》2000,21(9):1681-1687
BACKGROUND AND PURPOSE: Esophageal invasion (EI) by head and neck neoplasm has important prognostic and surgical management implications. Our purpose was to determine the accuracy of MR imaging for predicting neoplastic cervical esophageal invasion. METHODS: MR scans of the neck obtained from 22 patients with periesophageal masses were retrospectively reviewed independently and by consensus by two experienced head and neck radiologists who were unaware of surgical findings. The patients were selected from clinical, radiologic, or pathologic reports suggesting EI. The following imaging criteria for EI were evaluated: effacement of periesophageal fat planes, circumferential mass, paraesophageal lymph nodes, luminal size, wall thickening, increased T2 wall signal, and wall enhancement. There were eight patients with EI and 14 patients without EI, as confirmed by surgical findings or pathologic examination. RESULTS: The consensus criteria with the best sensitivities were any wall thickening (100%), effaced fat plane (100%), and any T2 wall signal abnormality (100%). The criteria with the best specificities were circumferential mass greater than 270 (100%) or 180 degrees (93%) and focal T2 wall signal abnormality (86%). The overall kappa value for the two readers for all criteria was 0.57 (moderate agreement). CONCLUSION: A circumferential mass or focal T2 signal abnormality on the esophageal wall suggests the presence of EI. An intact fat plane, absence of wall thickening, and no T2 wall signal abnormalities imply that the esophagus is not invaded. 相似文献