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排序方式: 共有302条查询结果,搜索用时 31 毫秒
21.
22.
Prolonged survival of porcine hepatocytes in cynomolgus monkeys 总被引:3,自引:0,他引:3
Nagata H Nishitai R Shirota C Zhang JL Koch CA Cai J Awwad M Schuurman HJ Christians U Abe M Baranowska-Kortylewicz J Platt JL Fox IJ 《Gastroenterology》2007,132(1):321-329
BACKGROUND & AIMS: Management of patients with liver failure can be a significant medical challenge, and transplantation of the liver is the only definitive therapy. Whole liver allotransplantation is limited by a shortage of human donors and the risks of the surgery in those most ill. Transplants consisting of xenogeneic hepatocytes might overcome these problems, and work in rodents indicates that such transplants can correct some metabolic deficiencies and can prevent the complications and mortality associated with hepatic failure. As a prelude to clinical application, we tested the feasibility of hepatocyte xenotransplantation in nonhuman primates. METHODS: One to 2 billion hepatocytes from outbred swine were transplanted into the spleens of cynomolgus monkeys using conventional immunosuppression to control rejection. Duration of graft function was determined based on assay for porcine albumin. RESULTS: Following a single infusion, xenogeneic hepatocytes functioned for more than 80 days and, following re-transplantation, for more than 253 days. Engraftment in the spleen was confirmed 40 days after transplantation by asialoglycoprotein receptor-directed nuclear scanning. The humoral immune response to the transplanted porcine cells had no discernible impact on the survival of the grafts. CONCLUSIONS: Xenotransplantation of hepatocytes should be explored as a readily available, minimally invasive form of therapy for hepatic failure. 相似文献
23.
Background.
Currently, only Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status is used as a decisional marker for epidermal growth factor receptor (EGFR) inhibitor therapy in colorectal cancer (CRC) patients. Concordance of KRAS status between primary tumors and metastases has always been considered to be close to perfect; however, cases of discordance have been reported. The actual rate of concordance of KRAS status remains unclear, as is the same for v-raf murine sarcoma viral oncogene homolog B1 (BRAF), phosphatidylinositol 3-kinase CA subunit (PIK3CA), and loss of phosphatase and tensin homologue deleted on chromosome ten (PTEN). Therefore, it is unknown whether it is necessary to perform mutational analysis on metastases instead of on (or in addition to) primary tumors.Design.
A systematic literature search was conducted to collect all studies testing concordance of KRAS in CRC, and also of BRAF, PIK3CA, and loss of PTEN.Results.
Twenty-one studies have reported concordance of KRAS, with an overall concordance rate of 93% (range, 76%–100%). Overall concordance rates of studies testing concordance of BRAF status and loss of PTEN were 98% and 68%, respectively. Three studies reported concordance of PIK3CA status (range, 89%–94%).Conclusion.
Though discordance of KRAS status does occur, it is uncommon. When considering the downsides of testing metastatic tissue in all patients along with the low incidence of discordance, we conclude that that testing the primary tumor (or whatever tissue available) is sufficient for clinical decision making on EGFR inhibitor therapy. 相似文献24.
Padmos RC Schloot NC Beyan H Ruwhof C Staal FJ de Ridder D Aanstoot HJ Lam-Tse WK de Wit H de Herder C Drexhage RC Menart B Leslie RD Drexhage HA;LADA Consortium 《Diabetes》2008,57(10):2768-2773
OBJECTIVE—There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes.RESEARCH DESIGN AND METHODS—We studied patterns of inflammatory gene expression in monocytes of patients with type 1 diabetes (juvenile onset, n = 30; adult onset, n = 30) and latent autoimmune diabetes of the adult (LADA) (n = 30) (controls subjects, n = 49; type 2 diabetic patients, n = 30) using quantitative PCR. We tested 25 selected genes: 12 genes detected in a prestudy via whole-genome analyses plus an additional 13 genes identified as part of a monocyte inflammatory signature previously reported.RESULTS—We identified two distinct monocyte gene expression clusters in autoimmune diabetes. One cluster (comprising 12 proinflammatory cytokine/compound genes with a putative key gene PDE4B) was detected in 60% of LADA and 28% of adult-onset type 1 diabetic patients but in only 10% of juvenile-onset type 1 diabetic patients. A second cluster (comprising 10 chemotaxis, adhesion, motility, and metabolism genes) was detected in 43% of juvenile-onset type 1 diabetic and 33% of LADA patients but in only 9% of adult-onset type 1 diabetic patients.CONCLUSIONS—Subgroups of type 1 diabetic patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of autoimmune diabetes only partly overlapping with the presently known diagnostic categories.There is evidence that monocytes of patients with type 1 diabetes are functionally aberrant, showing raised production of interleukin (IL)-1β, IL-6, superoxide anion, and prostaglandin-endoperoxide synthase 2 (PTGS2) (1–3); aberrant generation of antigen-presenting cells (4,5); and abnormal chemotaxis, adhesion, and migratory potential (6). These aberrancies are thought to play a role in the pathogenesis of the disease by disrupting tolerance and aggravating the β-cell cytotoxic potential of infiltrating monocyte-derived dendritic cells and macrophages. However, these aberrant functional findings could not always be reproduced, particularly with regard to the enhanced production of PTGS2 (7) and the poor generation of antigen-presenting cells from monocytes (8). Two issues could be relevant to these discrepancies. First, raised production of proinflammatory monocyte-derived cytokines could be related to hyperglycemia (9). Second, there might be heterogeneity within autoimmune diabetes, such as has been noted previously between adult and juvenile forms of type 1 diabetes on the basis of genetic, immune, and metabolic characteristics (10). This possible heterogeneity in autoimmune diabetes might also become evident in different monocyte activation profiles.To resolve these issues, we focus here on patterns of inflammatory gene expression in monocytes from selected patients distinguished by clinical characteristics and age at diagnosis, as well as from control subjects. Our hypothesis is that monocytes might be distinctly activated and disturbed within the known diagnostic categories of diabetes.Recently, we reported a signature of 18 inflammatory-related genes in monocytes of bipolar patients (11); activated monocytes are thought to play a role in the pathogenesis of bipolar disorder (12,13). Given the reported association between bipolar disorder and autoimmune diabetes (14), and given the possible central role of monocytes in both disorders, we tested this set of 18 proinflammatory monocyte genes in patients with autoimmune diabetes. To these 18 monocyte genes, we added 7 genes identified in a whole-genome expression profile of a set of juvenile-onset type 1 diabetic patients who had been compared with healthy control subjects and type 2 diabetic patients (see supplementary Fig. 1 [available in an online appendix at http://dx.doi.org/10.2337/db08-0496]). Thus, using quantitative RT-PCR (Q-PCR), we validated abnormal expression of 25 monocyte activation genes in latent autoimmune diabetes of the adult (LADA), adult-onset type 1 diabetic and juvenile-onset type 1 diabetic patients, and, as controls, type 2 diabetic patients and healthy subjects.Open in a separate windowFIG. 1.Color-coded correlation matrix illustrating pairwise correlations between the expression levels of the 24 genes aberrantly expressed in patients with various forms of diabetes (相似文献
25.
Ruben F. Kranenburg Henk-Jan Ramaker Sharon Sap Arian C. van Asten 《Drug testing and analysis》2022,14(6):1089-1101
Both the increasing number and diversity of illicit-drug seizures complicate forensic drug identification. Traditionally, colorimetric tests are performed on-site, followed by transport to a laboratory for confirmatory analysis. Higher caseloads increase laboratory workload and associated transport and chain-of-evidence assurance performed by police officers. Colorimetric tests are specific only for a small set of drugs. The rise of new psychoactive substances therefore introduces risks for erroneous results. Near-infrared (NIR)-based analyzers may overcome these encumbrances by their compound-specific spectral selectivity and broad applicability. This work introduces a portable NIR analyzer that combines a broad wavelength range (1300–2600 nm) with a chemometric model developed specifically for forensic samples. The application requires only a limited set of reference spectra for time-efficient model training. This calibration-light approach thus eliminates the need of extensive training sets including mixtures. Performance was demonstrated with 520 casework samples resulting in a 99.6% true negative and 97.6% true positive rate for cocaine. Similar results were obtained for MDMA, methamphetamine, ketamine, and heroin. Additionally, 236 samples were analyzed by scanning directly through their plastic packaging. Also here, a >97% true positive rate was obtained. This allows for non-invasive, operator-safe chemical identification of potentially potent drugs of abuse. Our results demonstrate the applicability for multiple drug-related substances. Ideally, the combination of this NIR approach with other portable techniques, such as Raman and IR spectroscopy and electrochemical tests, may eventually eliminate the need for subsequent laboratory analysis; therefore, saving tremendous resources in the overall forensic process of confirmatory illicit drug identification. 相似文献
26.
27.
Computer-controlled infusion of ORG 21465, a water soluble steroid i.v. anaesthetic agent, into human volunteers 总被引:2,自引:2,他引:0
Sneyd J. R.; Wright PMC.; Harris D.; Taylor P. A.; Vijn PCM.; Cross M.; Dale H.; Voortman G.; Boen P. 《British journal of anaesthesia》1997,79(4):433-439
ORG 21465 has been found to possess anaesthetic properties in humans and
its pharmacokinetics are known. We performed this study to confirm the
characteristics associated with its administration and to define its
pharmacodynamic profile, in particular to explore the relationship between
sedation, anaesthesia, excitation and plasma drug concentrations. A water
soluble preparation of ORG 21465 was administered to six male volunteers as
a series of three 15-min computer-controlled, pharmacokinetic model-driven
infusions targeting three exponentially increasing plasma concentrations:
0.5, 1 and 2 micrograms ml-1. The clinical characteristics of the resultant
sedation and anaesthesia were observed. Plasma concentrations of ORG 21465
were measured during and for 500 min after the infusions and the EEG
recorded. A sigmoid e-max effect compartment pharmacodynamic model was
fitted to the plasma concentrations and an EEG derivative (spectral edge
frequency (SEF)). Anaesthesia with ORG 21465 was associated with
involuntary movements in all subjects. A steady state concentration of 1180
ng ml-1 depressed SEF by 50%, the Hill factor describing the sigmoid nature
of the concentration-response curve was 1.42 and the equilibration rate
constant of the biophase was 0.112 min-1. Anaesthesia with ORG 21465 was
found to be unsatisfactory because of involuntary movements and slow
equilibration with the biophase.
相似文献
28.
Kerkhoffs GM van den Bekerom M Elders LA van Beek PA Hullegie WA Bloemers GM de Heus EM Loogman MC Rosenbrand KC Kuipers T Hoogstraten JW Dekker R Ten Duis HJ van Dijk CN van Tulder MW van der Wees PJ de Bie RA 《British journal of sports medicine》2012,46(12):854-860
Ankle injuries are a huge medical and socioeconomic problem. Many people have a traumatic injury of the ankle, most of which are a result of sports. Total costs of treatment and work absenteeism due to ankle injuries are high. The prevention of recurrences can result in large savings on medical costs. A multidisciplinary clinical practice guideline was developed with the aim to prevent further health impairment of patients with acute lateral ankle ligament injuries by giving recommendations with respect to improved diagnostic and therapeutic opportunities. The recommendations are based on evidence from published scientific research, which was extensively discussed by the guideline committee. This clinical guideline is helpful for healthcare providers who are involved in the management of patients with ankle injuries. 相似文献
29.
Ham SJ de Lange J van der Zwan AL Schaap GR van der Woude HJ Heeg M 《Nederlands tijdschrift voor geneeskunde》2012,156(11):A4254
Multiple osteochondroma, also known as hereditary multiple exostoses, is a relatively rare genetic disorder characterized by the presence of multiple osteochondromas. The disease is frequently painful, with restriction of the activities of daily living, problems with carrying out an occupation and performance at school. In addition, characteristic skeletal deformities and postural abnormalities of the joints very frequently occur in patients with this disorder. Malignant transformation of osteochondroma to chondrosarcoma occurs in 1-5% of the patients with multiple osteochondroma. Treatment of patients with multiple osteochondromas must be tuned to the problems experienced by the patient. Symptomatic osteochondromas are often an indication for excision; knowledge of the natural progression of the abnormality is important in this. Periodical screening is essential: in children to prevent or correct deformity and postural abnormalities and in adults to detect and treat malignant transformation of osteochondroma at an early stage. 相似文献
30.
Marije Slingerland Henk-Jan Guchelaar Hilde Rosing Max E. Scheulen Laurence J.C. van Warmerdam Jos H. Beijnen Hans Gelderblom 《Clinical therapeutics》2013