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1.
M Debono K E Willard H A Kirst J A Wind G D Crouse E V Tao J T Vicenzi F T Counter J L Ott E E Ose 《The Journal of antibiotics》1989,42(8):1253-1267
A series of 20-deoxo-20-cyclic (alkylamino) derivatives of tylosin, desmycosin, macrocin and lactenocin was prepared by reductive amination of the C-20 aldehyde group. The majority of the compounds were prepared using metal hydrides (sodium cyanoborohydride or sodium borohydride) as the reducing agents and a suitable cyclic alkylamine. Subsequently, a more convenient procedure was developed using formic acid as a reducing agent. The C-20 amino derivatives prepared from desmycosin exhibited good in vitro antimicrobial activity against Pasteurella haemolytica and Pasteurella multocida (MIC range of 0.78 approximately 6.25 micrograms/ml) as well as Mycoplasma species (MIC range of 0.39 approximately 6.25 micrograms/ml). Several derivatives showed excellent oral efficacy against infections caused by P. multocida in chicks. One of these derivatives, 20-deoxo-20-(3,5-dimethylpiperidin-1-yl)desmycosin (tilmicosin or EL-870) was selected for development as a therapeutic agent for pasteurellosis in calves and pigs. 相似文献
2.
Bradley Q. Fox Peninah F. Benjamin Ammara Aqeel Emily Fitts Spencer Flynn Brian Levine Elizaveta Maslak Rebecca L. Milner Benjamin Ose Michael Poeschla Meghna Ray Maeve Serino Sahaj S. Shah Kelly L. Close 《Clinical Diabetes》2021,39(2):160
To the best of our knowledge, there are no published data on the historical and recent use of CGM in clinical trials of pharmacological agents used in the treatment of diabetes. We analyzed 2,032 clinical trials of 40 antihyperglycemic therapies currently on the market with a study start date between 1 January 2000 and 31 December 2019. According to ClinicalTrials.gov, 119 (5.9%) of these trials used CGM. CGM usage in clinical trials has increased over time, rising from <5% before 2005 to 12.5% in 2019. However, it is still low given its inclusion in the American Diabetes Association’s latest guidelines and known limitations of A1C for assessing ongoing diabetes care.The availability of reliable continuous glucose monitoring (CGM) systems has proven to be a major innovation in diabetes management and research. Most current CGM systems are approved for 7- to 14-day use and use a wire-tipped glucose oxidase sensor inserted in subcutaneous tissue to monitor glucose concentrations in interstitial fluid. One implanted CGM system is approved for longer-term use (90–180 days); it operates with fluorescence-based technology. CGM sensors record a glucose data point every 1–15 minutes (depending on the system), collecting far more granular data and information on glycemic patterns than self-monitoring of blood glucose (SMBG) alone. Real-time CGM or intermittently scanned CGM systems send data continuously or intermittently to dedicated receivers or smartphones, whereas professional CGM systems provide retrospective data, either blinded or unblinded, for analysis and can be used to identify patterns of hypo- and hyperglycemia. Professional CGM can be helpful to evaluate patients when other CGM systems are not available to the patient or the patient prefers a blinded analysis or a shorter experience with unblinded data.In the 20 years since CGM systems first became available to people with diabetes, technological improvements, particularly pertaining to accuracy and form factor, have made CGM increasingly viable for both patient use and clinical investigation (1,2). Average sensor MARD (mean absolute relative difference; a summary accuracy statistic) has decreased from >20 to <10% (3–10), including two systems that do not require fingerstick calibrations and three that are approved to be used for insulin dosing (11). Concurrently, size, weight, and cost of CGM systems have all decreased, while user-friendliness and convenience have increased (12).To encourage use of CGM-derived data, researchers and clinicians have worked to develop a standard set of glycemic metrics beyond A1C. In 2017, two international groups of leading diabetes clinical and research organizations published consensus definitions for key metrics, including clinically relevant glycemic cut points for hypoglycemia (<70 and <54 mg/dL), hyperglycemia (>180 and >250 mg/dL), and time in range (TIR; 70–180 mg/dL) (13,14).CGM-derived metrics provide far greater precision and granularity than is possible with SMBG or A1C data alone (Table 1), enabling clinicians and investigators to better represent inter- and intraday glycemic differences with metrics such as TIR, glycemic variability, and time in hypoglycemia and hyperglycemia (15). Crucially, CGM also allows for the accurate measurement and detection of nocturnal glycemia (16). The use of these metrics enables a more comprehensive understanding of glycemic management that can facilitate individualized treatment for people with diabetes or prediabetes. Although A1C is a useful estimate of mean glucose over the previous 2–3 months, especially when evaluating population health, it is important to include other glycemic outcomes in clinical trials. Furthermore, there is emerging evidence suggesting that TIR predicts the development of microvascular complications at least as well as A1C (17,18).TABLE 1Benefits of CGM Compared With A1C Alone in Assessing Glycemia
Open in a separate windowDespite recent standardization of metrics and an emerging consensus around the importance of including CGM-derived outcomes in clinical trials, to our knowledge, there has been no attempt to estimate the historical and current use of CGM in clinical trials of pharmacological agents for diabetes. We sought to analyze the use of CGM in trials of currently available pharmaceutical agents for the treatment of diabetes. 相似文献
CGM | A1C Alone |
---|---|
Facilitates real-time readings of blood glucose levels | Requires SMBG |
Provides information on glucose variability, including duration of hypo- and hyperglycemia and nocturnal glycemia | Does not provide information on acute glycemic excursions and time in biochemical hypoglycemia and hyperglycemia |
Correlates strongly with 3 months of mean glucose, TIR, and hyperglycemia metrics | Measures average glucose during the past 2–3 months |
Provides information on direction of and rate of change in glucose levels | Does not provide information on direction of or rate of change in glucose levels |
Provides TIR data (time spent between 70 and 180 mg/dL) | Does not have TIR measurement capability |
3.
Olaug K. Rødningen Oddveig Røshy Serena Tonstad Leiv Ose Kåre Berg Trond P. Leren 《Clinical genetics》1992,42(6):288-295
Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was performed in Norwegian subjects heterozygous for familial hypercholesterolemia (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and the restriction enzyme NcoI, showed that two out of 57 unrelated FH subjects had an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was due to a 9.6 kb deletion that included exons 16 and 17. The 5' deletion breakpoint was after 245 bp of intron 15, and the 3' deletion breakpoint was in exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane-spanning and cytoplasmatic domains of the receptor had been deleted. A polymerase chain reaction (PCR) method was developed to identify this deletion among other Norwegian FH subjects. As a result of this screening one additional subject was found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated Norwegian FH subject possessed this deletion. The deletion was found on the same haplotype in the three unrelated subjects, suggesting a common mutagenic event. The deletion is identical to a deletion (FH-Helsinki) that is very common among Finnish FH subjects. However, it is not yet known whether the mutations evolved separately in the two countries. 相似文献
4.
Lee MH Gordon D Ott J Lu K Ose L Miettinen T Gylling H Stalenhoef AF Pandya A Hidaka H Brewer B Kojima H Sakuma N Pegoraro R Salen G Patel SB 《European journal of human genetics : EJHG》2001,9(5):375-384
Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM. 相似文献
5.
Yoshitada Yoshioka Hisamitsu Nagase Youki Ose Takahiko Sato 《Ecotoxicology and environmental safety》1986,12(3):206-212
The test method of "activated sludge, respiration inhibition test" proposed by the OECD was critically carried out and compared with other test methods. Investigation of test conditions showed that the moderate deviation from the test conditions defined by the OECD Test Guidelines did not have much effect on the result, and some modifications were proposed to improve the method. This method had a poor detection limit compared with the LC50 test with Oryzias latipes and EC50 of the growth inhibition test with Tetrahymena pyriformis. The susceptivity of the method was particularly poor for the chemicals which were highly toxic in the other two tests. 相似文献
6.
Ryu Kanzaki Eriko Fukui Takashi Kanou Naoko Ose Soichiro Funaki Masato Minami Yasushi Shintani Meinoshin Okumura 《Journal of thoracic disease》2021,13(4):2590
Pulmonary metastasectomy (PM) is an established treatment that can provide improved long-term survival for patients with metastatic tumor(s) in the lung. In the current era, where treatment options other than PM such as stereotactic body radiation therapy (SBRT), immunotherapy, and molecular-targeted therapy are available, thoracic surgeons should review the approach to the preoperative evaluation and the indications. Preoperative evaluation consists of history and physical examinations, physiological tests, and radiological examinations. Radiological examinations serve to identify the differential diagnosis of the pulmonary nodules, evaluate their precise number, location, and features, and search for extra thoracic metastases. The indication of PM should be considered from both physiological and oncological points of view. The general criteria for PM are as follows; (I) the patient has a good general condition, (II) the primary malignancy is controlled, (III) there is no other extrapulmonary metastases, and (IV) the pulmonary lesion(s) are thought to be completely resectable. In addition to the general eligibility criteria of PM, prognostic factors of each tumor type should be considered when deciding the indication for PM. When patients have multiple poor prognostic factors and/or a short disease-free interval (DFI), thoracic surgeons should not hesitate to observe the patient for a certain period before deciding on the indication for PM. A multidisciplinary discussion is needed in order to decide the indication for PM. 相似文献
7.
Kento Takatori Kazuki Terashima Rihito Yoshida Aya Horai Shinya Satake Takayuki Ose Naoto Kitajima Yoshikazu Kinoshita Yusuke Demizu Nobukazu Fuwa 《Journal of gastroenterology》2014,49(6):1074-1080
Background
Little is known about acute upper gastrointestinal (GI) complications associated with gemcitabine-concurrent proton radiotherapy (GPT) for inoperable pancreatic cancer. We investigated acute GI complications following GPT in patients with inoperable pancreatic cancer using small-bowel endoscopy.Methods
This prospective single center observational study was conducted at the Hyogo Ion Beam Medical Center from January 2010 to January 2012. Ninety-one patients who had clinically and medically inoperable pancreatic cancer treated by GPT were analyzed. Endoscopic examinations were performed before and after GPT to clarify the incidence rates of radiation-induced ulcers, GI hemorrhage, and GI perforation associated with GPT.Results
Post-treatment endoscopic examinations revealed that 45 (49.4 %) patients had radiation-induced ulcers in the stomach and duodenum. Of those, many ulcerative lesions were found in the lower stomach (51 %) and horizontal part of the duodenum (39 %), regardless of the primary tumor site in the pancreas. Neither GI hemorrhage, nor perforation, was found in post-treatment endoscopy examinations.Conclusion
Approximately half of the patients treated with GPT for inoperable pancreatic cancer exhibited radiation-induced ulcers in the stomach and duodenum. 相似文献8.
Tore Hofstad Jorun Rugksa Solveig O. Ose Olav Nyttingnes Tonje L. Husum 《International journal of methods in psychiatric research》2021,30(3)
ObjectiveA variety of measures are used for reporting levels of compulsory psychiatric hospitalisation. This complicates comparisons between studies and makes it hard to establish the extent of geographic variation. We aimed to investigate how measures based on events, individuals and duration portray geographical variation differently and perform over time, how they correlate and how well they predict future ranked levels of compulsory hospitalisation.MethodsSmall‐area analysis, correlation analysis and linear regressions of data from a Norwegian health registry containing whole population data from 2014 to 2018.ResultsThe average compulsory hospitalisation rate per 100,000 inhabitant was 5.6 times higher in the highest area, compared to the lowest, while the difference for the compulsory inpatient rate was 3.2. Population rates based on inpatients correlate strongly with rates of compulsory hospitalisations (r = 0.88) and duration (r = 0.78). 68%–81% of ranked compulsory hospitalisation rates could be explained by each area''s rank the previous year.ConclusionThere are stable differences in service delivery between catchment areas in Norway. In future research, multiple measures of the level of compulsory hospitalisation should ideally be included when investigating geographical variation. It is important that researchers describe accurately the measure upon which their results are based. 相似文献
9.
Irina Sominskaya Dace Skrastina Andris Dislers Denis Vasiljev Marija Mihailova Velta Ose Dzidra Dreilina Paul Pumpens 《Clinical and Vaccine Immunology : CVI》2010,17(6):1027-1033
A multivalent vaccine candidate against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was constructed on the basis of HBV core (HBc) virus-like particles (VLPs) as carriers. Chimeric VLPs that carried a virus-neutralizing HBV pre-S1 epitope corresponding to amino acids (aa) 20 to 47 in the major immunodominant region (MIR) and a highly conserved N-terminal HCV core epitope corresponding to aa 1 to 60 at the C terminus of the truncated HBcΔ protein (N-terminal aa 1 to 144 of full-length HBc) were produced in Escherichia coli cells and examined for their antigenicity and immunogenicity. The presence of two different foreign epitopes within the HBc molecule did not interfere with its VLP-forming ability, with the HBV pre-S1 epitope exposed on the surface and the HCV core epitope buried within the VLPs. After immunization of BALB/c mice, specific T-cell activation by both foreign epitopes and a high-titer antibody response against the pre-S1 epitope were found, whereas an antibody response against the HBc carrier was notably suppressed. Both inserted epitopes also induced a specific cytotoxic-T-lymphocyte (CTL) response, as shown by the gamma interferon (IFN-γ) production profile.Genetically engineered virus-like particle (VLP)-based vaccines are one of the most promising tools in modern vaccinology. VLPs from almost all classes of viruses are being evaluated now or have just been adopted to use as carriers for presentation of foreign immunological epitopes (for a review, see references 29 and 31). VLP technologies possess obvious advantages for the generation of safe and efficacious vaccines. First, the repetitive antigenic structure of VLPs makes them highly immunogenic. Second, VLPs lack viral genomes or genes and are noninfectious, although they mimic infectious viruses in their structural and immunological features. Third, VLPs are generated by highly efficient heterologous expression of the cloned viral structural genes with subsequent quantitative in vivo or in vitro self-assembly of their products. Fourth, VLPs can be obtained by simple and efficient purification procedures. VLPs can be used for a broad range of applications, but the generation of vaccines against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is of special interest.The HBV core (HBc) protein was first reported as a promising VLP carrier in 1986 and was published in 1987 (6, 10, 24). In many ways, HBc occupies a unique position among the VLP carriers because of its high-level synthesis and efficient self-assembly in virtually all known homologous and heterologous expression systems, including bacteria (for a review, see references 29 to 31). The major HBc B-cell epitopes (c and e1) are localized within the major immunodominant region (MIR), whereas the next important epitope, e2, is localized around amino acid position 130, close to the C-terminal histone-like region (for a review, see reference 30).The high-resolution spatial structure of HBc icosahedrons (11, 43) shows that the MIR is located on the tip of the spike, around the most protruding region between amino acids (aa) 78 and 82. For this reason, the MIR is generally accepted as the target site of choice for insertion of foreign epitopes (30). The other widely accepted site for insertions is C-terminal position 144, a short stretch after the e2 epitope. For C-terminal insertions, so-called HBcΔ vectors lacking a 39-aa-long positively charged C-terminal histone-like fragment are preferred for their high insertion capacities (up to 741 amino acid residues) (30).Here, we present the construction and preliminary immunological characterization of a first multivalent HBV and HCV vaccine candidate. As an HBV epitope, we chose the pre-S1 sequence aa 20 to 47, which alone is able to elicit HBV-neutralizing and protective antibodies (23), for insertion into the HBc MIR. Concurrently, we inserted at the C terminus of the HBcΔ vector the N-terminal 60-aa fragment of the HCV core, which is highly conserved among various HCV genotypes with amino acid homology exceeding 95% (12, 14) and therefore is an attractive target for the generation of an HCV vaccine (19, 41). Such a combination of foreign epitopes did not prevent correct self-assembly of chimeric HBc-based particles and provided them with specific HBV and HCV antigenicity and immunogenicity in mice. 相似文献
10.
The effects of orange flavoured colestipol granules, 10 g/day, in 37 boys and 29 girls aged 10-16 years with familial hypercholesterolaemia were examined first in an eight week double blind, placebo controlled protocol, then in open treatment for 44-52 weeks. All patients were on a low fat diet. Low density lipoprotein cholesterol levels were reduced by 19.5% by colestipol v 1.0% by placebo. Levels of serum folate, vitamin E, and carotenoids were reduced in the colestipol group, but not the vitamin E/cholesterol and carotenoid/cholesterol ratios or serum concentrations of vitamins A and D. After one year of colestipol, two thirds of the participants remained in the study, of whom half took > or = 80% of the prescribed dose. Those who took > or = 80% of the dose had a greater decrease in serum 25-hydroxyvitamin D levels than those who took < 80%. No adverse effects on weight gain or linear growth velocity were observed. Although low dose colestipol effectively reduces low density lipoprotein cholesterol levels, only a minority of adolescents adhered to the new formulation for one year. Folate and possibly vitamin D supplementation is recommended. 相似文献