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排序方式: 共有565条查询结果,搜索用时 15 毫秒
71.
Cui Y Koop EA van Diest PJ Kandel RA Rohan TE 《Breast cancer research and treatment》2007,104(1):103-107
Germ-line mutations in BRCA1 and BRCA2 are responsible for about 30–60% of the hereditary breast and ovarian cancer (HBOC). A large number of point mutations have
been described in both genes. However, large deletions and duplications that disrupt one or more exons are overlooked by point
mutation detection approaches. Over the past years several rearrangements have been identified in BRCA1, while few studies have been designed to screen this type of mutations in BRCA2. Our aim was to estimate the prevalence of large genomic rearrangements in the BRCA2 gene in Spanish breast/ovarian cancer families. The multiplex ligation-dependent probe amplification (MLPA) was employed
to search gross deletions or duplications of BRCA2 in 335 Spanish moderate to high-risk breast/ovarian cancer families previously screened negative for point mutations by conventional
methods. Four different and novel large genomic alterations were consistently identified by MLPA in five families, respectively:
deletions of exon 2, exons 10–12 and exons 15–16 and duplication of exon 20 (in two families). RT-PCR experiments confirmed
the deletion of exons 15–16. All patients harbouring a genomic rearrangement were members of high-risk families, with three
or more breast/ovarian cancer cases or the presence of breast cancer in males. We provide evidence that the BRCA2 rearrangements seem to account for a relatively small proportion of familial breast cancer cases in Spanish population. The
screening for these alterations as part of the comprehensive genetic testing can be recommended, especially in multiple case
breast/ovarian families and families with male breast cancer cases. 相似文献
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77.
L D Gruenke K Konopka D R Koop L A Waskell 《The Journal of pharmacology and experimental therapeutics》1988,246(2):454-459
A sensitive assay for trifluoroacetic acid, the major product of the oxidative metabolism of halothane, has been developed to study the biotransformation of halothane. A selected ion monitoring gas chromatographic mass spectrometric assay measured trifluoroacetic acid levels as low as 1 microM in 100 microliter of reaction mixture. This assay was used to quantitate halothane metabolism in human and rabbit microsomal systems and with purified proteins. Trifluoroacetic acid production was examined as a function of the concentration of substrate present, the amount of microsomal protein used and the length of reaction time. Halothane metabolism in microsomes was linear for at least 30 min, and up to a microsomal protein concentration of 1 mg/ml. In rabbits, phenobarbital and imidazole induced the microsomal metabolism of halothane 7.36- and 18.2-fold, respectively. Imidazole was used because it is a potent inducer of cytochrome P-450 isozyme 3a which is also induced by ethanol. The cytochrome P-450 in microsomes from a single human subject metabolized halothane at a rate comparable to that found in microsomes from phenobarbital- and imidazole-pretreated rabbits. The purified phenobarbital and imidazole inducible cytochromes P-450, isozymes 2 and 3a, catalyzed the oxidation of halothane to trifluoroacetic acid. Cytochrome b5 stimulated the isozyme 3a-catalyzed oxidation of halothane by 19-fold, whereas isozyme 2 catalyzed oxidation was increased 4.3-fold. Antibodies to cytochrome P-450 3a inhibited halothane metabolism by 90% in microsomes from imidazole-pretreated rabbits, suggesting that isozyme 3a catalyzes halothane metabolism in imidazole-pretreated rabbits. In conclusion, the oxidation of halothane to trifluoroacetic acid by cytochrome P-450 isozymes 3a and 2 is enhanced markedly by cytochrome b5. 相似文献
78.
Gehlsen U Oetke A Szaszák M Koop N Paulsen F Gebert A Huettmann G Steven P 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2012,250(9):1293-1302
Background
Early and correct diagnosis of delayed or absent corneal epithelial wound healing is a key factor in the prevention of infection and consecutive destruction of the corneal stroma with impending irreversible visual loss. Two-photon microscopy (TPM) is a novel technology that has potential to depict epithelial cells and to evaluate cellular function by measuring autofluorescence properties such as fluorescence intensity and fluorescence lifetimes of metabolic co-factors such as NAD(P)H.Methods
Using non-invasive TPM in a tissue-culture scratch model and an organ-culture erosion model, fluorescence intensity and fluorescence lifetimes of NAD(P)H were measured before and during closure of the epithelial wounds. Influence of temperature and selective inhibition of metabolism on intensity and lifetimes were tested additionally.Results
Decrease of temperature resulted in significant increase of fluorescence lifetimes and decrease of the relative amount of free NAD(P)H due to decreased global metabolism. Increase in temperature and upregulation of glycolysis through blocking the mitochondrial electron transport chain by rotenone resulted in increased intensity, decreased lifetimes and increase in the relative amount of free NAD(P)H. Changes of lifetimes and free:protein-bound NAD(P)H ratios were similar to changes measured during wound healing in both scratch and erosion models.Conclusions
Fluorescence lifetime measurements (FLIM) detected enhancement of cellular metabolism following epithelial damage in both models. The prospective detection of cellular autofluorescence in vivo, in particular FLIM of metabolic cofactor NAD(P)H, has the potential to become an indispensible tool in clinical use to differentiate healing from non-healing epithelial cells and to evaluate effects of newly developed substances on cellular metabolism in preclinical and clinical trials. 相似文献79.
Paul G. Lankisch M.D. Herbert Koop M.D. Jutta Otto 《The American journal of gastroenterology》1986,81(5):365-368
Using an inhibitor method, fasting levels of pancreatic isoamylase were measured in 46 healthy controls and in 218 patients undergoing a secretin-pancreozymin test for diagnostic purposes, and compared with immunoreactive trypsin (IRT). Exocrine pancreatic insufficiency was found in 82 of the patients. The specificity of both enzymes was high in patients with nonpancreatic diseases (pancreatic isoamylase: 98.5%, IRT: 96.3%). No patient with nonpancreatogenic steatorrhea had a low serum enzyme value. Sensitivity was, unfortunately, low in patients with exocrine pancreatic insufficiency (pancreatic isoamylase: 45.1%, IRT: 41.5%) and increased only slightly when patients after an acute attack of the disease, or patients with pseudocysts or older than 60 were excluded (pancreatic isoamylase: 67.9%, IRT: 58.5%). Although highly specific, pancreatic isoamylase measurement is not sensitive enough to be used as a screening test for exocrine pancreatic insufficiency but may be used to determine the etiology of steatorrhea. 相似文献
80.
Jürgensen JS Kettritz R Schneider W Koop H Hildebrand TS Frei U Eckardt KU 《Rheumatology international》2003,23(4):204-206
We describe a young woman whose initial presentation was dominated by acute diarrhoea. Life-threatening multiorgan failure rapidly ensued and necessitated mechanical ventilation and dialysis treatment. An initially elongated activated partial thromboplastin time prompted further coagulation tests that led to the detection of positive lupus anticoagulant, a highly elevated IgG-anticardiolipin (aCL) antibody titre, and prolonged dilute Russell's viper venom time. Histological examination of samples obtained during endoscopy revealed widespread intestinal thrombotic microangiopathy. In view of these serologic and histologic features, a diagnosis of the malignant variant of the antiphospholipid syndrome (APS), also termed 'catastrophic APS', was established. In spite of this syndrome's grim prognosis, the patient recovered following intensive anticoagulation and adjunct treatment with steroids and immunoglobulins. 相似文献