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31.
Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice 总被引:4,自引:3,他引:4
Lamb BT; Call LM; Slunt HH; Bardel KA; Lawler AM; Eckman CB; Younkin SG; Holtz G; Wagner SL; Price DL; Sisodia SS; Gearhart JD 《Human molecular genetics》1997,6(9):1535-1541
Missense mutations in the beta-amyloid precursor protein gene (APP) co-
segregate with a small subset of autosomal dominant familial Alzheimer's
disease (FAD) cases wherein deposition of the 39-43 amino acid beta-amyloid
(A beta) peptide and neurodegeneration are principal neuropathological
hallmarks. To accurately examine the effect of missense mutations on APP
metabolism and A beta production in vivo, we have introduced yeast
artificial chromosomes (YACs) containing the entire approximately 400 kbp
human APP gene encoding APP harboring either the asparagine for lysine and
leucine for methionine FAD substitution at codons 670 and 671
(APP(K670N/M671L)), the isoleucine for valine FAD substitution at codon 717
(APP(V7171)) or a combination of both substitutions into transgenic mice.
We demonstrate that, relative to YAC transgenic mice expressing wild-type
APP, high levels of A beta peptides are detected in the brains of YAC
transgenic mice expressing human APP(K670N/M671L) that is associated with a
concomitant diminution in the levels of apha-secretase-generated soluble
APP derivatives. Moreover, the levels of longer A beta peptides (species
terminating at amino acids 42/43) are elevated in YAC transgenic mice
expressing human APP(V7171). These mice should prove valuable for detailed
analysis of the in vivo effects of the APP FAD mutations in a variety of
tissues and throughout aging and for testing therapeutic agents that
specifically alter APP metabolism and A beta production.
相似文献
32.
Background
The study was performed to investigate the association of psychological stress and quality of life (QOL) among patients with the cardiovascular disease (CVD) of hypertension plus stroke or hypertension only. 相似文献33.
AC Robinson FRCS J Hanif FRCS LA Dumbreck MA MSC AJ Prichard FRCS BT Manners FRCPath MRCP 《International journal of clinical practice》1997,51(3):138-139
We have estimated that in 1995 more than £2 million was spent by the National Health Service on throat swabs used to investigate chronic tonsillitis in the UK. This study was devised to assess the value of this investigation. The surface microflora, obtained using a throat swab, was compared with the microflora of the deep tonsil in 30 cases of chronic tonsillitis. None of the throat swabs grew pathogenic organisms, while in 16 cases, heavy growths of recognised pathogens were grown from the tonsillar tissue. This paper demonstrates that throat swabs have little value in the management of chronic tonsillitis, and if the investigation was omitted in this condition, a substantial saving could be made. 相似文献
34.
DR Yates RK Safdar PA Spencer BT Parys 《Annals of the Royal College of Surgeons of England》2009,91(7):570-577
INTRODUCTION
Percutaneous nephrolithotomy (PCNL) is the first-line treatment for large and complex renal calculi. Accepted UK practice is to insert a nephrostomy tube at the end of the procedure to drain the kidney and reduce potential complications. ‘Tubeless’ or ‘nephrostomy-free’ PCNL has been advocated in selected patients as it is thought to reduce length of hospital stay, analgesia requirements and pain experienced. We present our outcomes of a consecutive series (n = 101) of ‘nephrostomy-free’ PCNLs compared to standard PCNL over a 4-year period.PATIENTS AND METHODS
Between January 2004 and October 2006, we performed 55 standard (with nephrostomy tube) PCNLs (Group 1). From October 2006 onwards, we changed our technique and have performed 46 consecutive ‘nephrostomy-free’ PCNLs (JJ stent inserted), independent of patient and stone factors (Group 2). We have compared the two groups in terms of length of hospital stay (LOS), analgesia requirements, transfusion rates, haemoglobin (Hb) decrease and immediate, early and late complications.RESULTS
‘Nephrostomy-free’ PCNL significantly reduced the length of hospital stay (2.8 vs 5.1 days; P < 0.001), morphine-based analgesia requirements (23% no morphine required vs 2.8%; P < 0.001), transfusion rate (2.5% vs 7%; P < 0.01) and mean Hb decrease (1.89 g/dl vs 2.25 g/dl; P > 0.05). Overall, no patient experienced a serious complication. All attempted ‘nephrostomy-free’ PCNLs were completed (stone clearance 95%) and no patient needed an unplanned nephrostomy. Only 5% in Group 2 needed their ureteric JJ stent removing earlier than planned secondary to pain. Both groups were comparable in terms of immediate, early and late complications, though three patients in Group 1 developed chronic loin pain and one patient in the ‘nephrostomy-free’ group developed a delayed perirenal haematoma.CONCLUSIONS
‘Nephrostomy-free’ percutaneous nephrolithotomy is a safe, effective and feasible procedure independent of patient and stone factors. It decreases the length of hospital stay, the pain experienced and the need for morphine-based analgesia; we feel it should be the standard of care for patients undergoing a PCNL. 相似文献35.
Anne JH Vochteloo DieuDonné Niesten Roeland Riedijk Willard J Rijnberg Stefan BT Bolder Sander Koëter Kremers-van de Keetie Hei Taco Gosens Peter Pilot 《BMC musculoskeletal disorders》2009,10(1):56-5
Background
A discussion is ongoing whether displaced femoral neck fractures in elderly patients should be treated with a non-cemented or a cemented hemiarthroplasty. A recent Cochrane analysis stresses the importance of further research into the relative merits of these techniques. We hypothesise that non-cemented hemiarthroplasty will result in at least the same technical-functional outcome and complication rate, with a shorter operation time. 相似文献36.
Y Liu D Kim BT Himes SY Chow T Schallert M Murray A Tessler I Fischer 《The Journal of neuroscience》1999,19(11):4370-4387
Adult mammalian CNS neurons do not normally regenerate their severed axons. This failure has been attributed to scar tissue and inhibitory molecules at the injury site that block the regenerating axons, a lack of trophic support for the axotomized neurons, and intrinsic neuronal changes that follow axotomy, including cell atrophy and death. We studied whether transplants of fibroblasts genetically engineered to produce brain-derived neurotrophic factor (BDNF) would promote rubrospinal tract (RST) regeneration in adult rats. Primary fibroblasts were modified by retroviral-mediated transfer of a DNA construct encoding the human BDNF gene, an internal ribosomal entry site, and a fusion gene of lacZ and neomycin resistance genes. The modified fibroblasts produce biologically active BDNF in vitro. These cells were grafted into a partial cervical hemisection cavity that completely interrupted one RST. One and two months after lesion and transplantation, RST regeneration was demonstrated with retrograde and anterograde tracing techniques. Retrograde tracing with fluorogold showed that approximately 7% of RST neurons regenerated axons at least three to four segments caudal to the transplants. Anterograde tracing with biotinylated dextran amine revealed that the RST axons regenerated through and around the transplants, grew for long distances within white matter caudal to the transplant, and terminated in spinal cord gray matter regions that are the normal targets of RST axons. Transplants of unmodified primary fibroblasts or Gelfoam alone did not elicit regeneration. Behavioral tests demonstrated that recipients of BDNF-producing fibroblasts showed significant recovery of forelimb usage, which was abolished by a second lesion that transected the regenerated axons. 相似文献
37.
Repeated injections of cocaine and morphine in laboratory rats cause a variety of molecular neuroadaptations in the cAMP signaling pathway in nucleus accumbens and ventral tegmental area. Here we report similar neuroadaptations in postmortem tissue from the brains of human smokers and former smokers. Activity levels of two major components of cAMP signaling, cAMP-dependent protein kinase A (PKA) and adenylate cyclase, were abnormally elevated in nucleus accumbens of smokers and in ventral midbrain dopaminergic region of both smokers and former smokers. Protein levels of the catalytic subunit of PKA were correspondingly higher in the ventral midbrain dopaminergic region of both smokers and former smokers. Protein levels of other candidate neuroadaptations, including glutamate receptor subunits, tyrosine hydroxylase, and other protein kinases, were within normal range. These findings extend our understanding of addiction-related neuroadaptations of cAMP signaling to tobacco smoking in human subjects and suggest that smoking-induced brain neuroadaptations can persist for significant periods in former smokers. 相似文献
38.
39.
Huang MT; Lou YR; Xie JG; Ma W; Lu YP; Yen P; Zhu BT; Newmark H; Ho CT 《Carcinogenesis》1998,19(9):1697-1700
Female Sencar mice (6 weeks old) were administered 1 mg of 7,12-
dimethylbenz[a]anthracene (DMBA) by oral gavage once a week for 5 weeks. At
20 weeks after the first dose of DMBA, 68% of mice developed mammary tumors
(the average 1.08 tumors per mouse) and 45% had lymphomas/leukemias.
Feeding 1% dibenzoylmethane (DBM) in AIN 76A diet, starting at 2 weeks
before the first dose of DMBA and continuing until the end of the
experiment, inhibited both the multiplicity and incidence of DMBA-induced
mammary tumor by 97%. The incidence of lymphomas/leukemias was completely
inhibited by 1% DBM diet. In contrast, feeding 2% curcumin diet had little
or no effect on the incidence of mammary tumors, and the incidence of
lymphomas/leukemias was reduced by 53%.
相似文献
40.
AJIW Bergman IET van den Berg W Brink BT Poll-The JK Ploos van Amstel R Berger 《Human mutation》1998,12(1):19-26
Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a deficient activity of the enzyme fumarylacetoacetase (FAH). To investigate the molecular heterogeneity of tyrosinemia, the geographic distribution and the genotype–phenotype relationship, we have analyzed the FAH genotype of 25 HT1 patients. Mutation screening was performed by PCR amplification of exons 1-14 of the FAH gene, followed by SSCP analysis and direct sequencing of the amplified exons. Fourteen different mutations were found, of which seven were novel, viz. Three missense mutations (G158D, P261L, F405H), a deletion of three nucleotides causing a deletion of serine (DEL366S) and three splice site mutations: IVS2+1(g-t), IVS6-1(g-c), IVS8-1(g-c). The splice site mutations IVS6-1(g-t) and IVS12+5(g-a) were frequently found in countries around the Mediterranean and northerwestern Europe, respectively. No clear correlation between the genotype and the three major HT1 subtypes could be established. Hum Mutat 12:19–26, 1998. © 1998 Wiley-Liss, Inc. 相似文献