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G K Scriba J A Hower N Y Liang P V Fennessey R T Borchardt 《The Journal of pharmacology and experimental therapeutics》1988,247(2):609-616
The effect of ibopamine (IBO) (SB 7505, SK&F 100168-A), a new drug for the treatment of congestive heart failure, and its active metabolite epinine (EPN) (N-methyldopamine), on the catecholamine content of hypothalamus and brainstem was studied in vitro after monoamine oxidase inhibition with pargyline. IBO and EPN increased levels of epinephrine (EPI) in a concentration- and time-dependent manner in both brain areas without significantly affecting the concentration of other catecholamines. Inhibition of either dopamine beta-hydroxylase, the neuronal EPI and norepinephrine uptake system, or esterase hydrolysis of IBO prevented the increase of EPI, whereas inhibition of phenylethanolamine N-methyltransferase, enzymatic dealkylation or the neuronal dopamine or serotonin uptake system had no influence on the increase of EPI levels. These results suggest that IBO after hydrolysis to EPN can be converted enzymatically to EPI by dopamine beta-hydroxylase in hypothalamus and brainstem. EPN seems to be accumulated into adrenergic and noradrenergic neurons by the high affinity uptake system. Changes in the EPI content of the central nervous system neurons might be responsible for some of the pharmacologic effects of IBO. 相似文献
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Phenytoin–lipid conjugates obtained by covalent binding of hydroxymethylphenytoin to diacylglycerides and to 3-acyloxy-2-acyl-oxymethylpropionic acids formed dispersions with a particle size of 10–200 µm when briefly sonicated in a sodium taurodeoxycholate-containing ethanol–water mixture. In contrast to the corresponding bis-deacyl derivatives, the lipids were not significantly hydrolyzed in aqueous buffers and in plasma. Incubation with pancreatic lipase yielded primarily the bis-deacyl compounds, which are comparable to monoglycerides, and subsequently liberated phenytoin. The glyceride-derived prodrugs were better substrates for the enzyme than the 3-acyloxy-2-acyloxymethyl-propionic acid derivatives. It is concluded that the phenytoin lipid conjugates are hydrolyzed by pancreatic lipase in a similar manner as natural triglycerides. 相似文献
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P. C. Scriba R. Landgraf H. G. Heinze und K. Schwarz 《Journal of molecular medicine (Berlin, Germany)》1966,44(2):69-76
Zusammenfassung 1. Es wird eine Methode zur gleichzeitigen Bestimmung des sog. freien und des proteingebundenen Anteils von in vitro zugesetztem L-Trijodthyronin-131Jod im Serum mittels Dextran-Gel-Filtration angegeben. In der beschriebenen Form ist diese Technik für die routinemäßige Anwendung in der Klinik zur Bestimmung der Bindungs- und Transportverhältnisse von Trijodthyronin geeignet.2. In sog. Verdrängungsversuchen wurde nichtmarkiertes Trijodthyronin dem Inkubationsgemisch von Serum und L-Trijodthyronin-131Jod zugesetzt. Die zugesetzten Trijodthyroninmengen erschöpfen die Gesamtbindungskapazität der Serumproteine in dem gewählten Konzentrationsbereich keineswegs. Im Gegensatz zum Verhalten der prozentualen Anteile des sog. freien und des proteingebundenen Trijodthyronins steigt die absolute Menge des proteingebundenen Trijodthyronins dabei steil an. Man findet eine Kurve, die nicht einer einfachen Sättigunskurve entspricht, sondern eine Resultante aus Sättigungskurven verschiedener Trijodthyronin-bindender Proteine und Verdrängungskurven kompetitiv gebundener Substanzen (z.B. Thyroxin) darstellt.3. Dextran-Gel wirkt nicht als einfaches Molekülsieb für Trijodthyronin. Es greift vielmehr durch Adsorptionsvorgänge kompetitiv in die Serumproteinbindungsverhältnisse des Trijodthyronins ein. Die physiologische Bedeutung des sog. freien Anteils an Trijodthyronin wird diskutiert.4. Die Methode zur Bestimmung des proteingebundenen Jods (PB127I) mittels alkalischer offener Veraschung (Barker) wurde technisch vereinfacht und bezüglich ihrer Reproduzierbarkeit untersucht. Die131Jodausbeute aus zugesetztem L-Thyroxin-131Jod lag bei diesem Verfahren bei ca. 80%.
Mit Unterstützung der Deutschen Forschungsgemeinschaft.
Herrn Prof. Dr. Dr. h. c.Carl Krauspe in Verehrung zum 70. Geburtstag gewidmet. 相似文献
Summary 1. A method allowing the simultaneous determination in serum of the socalled free and the protein bound part of 1-triiodothyronine-131I added in vitro, using dextran gel filtration, is presented. Assessment of serum protein binding and transport of triiodothyronine can be conveniently performed for clinical purposes by this procedure.2. In socalled discharge experiments non-labelled triiodothyronine is added to incubation mixtures of serum and l-triiodothyronine-131I. The amount of added triiodothyronine did not exhaust the total binding capacity of serum proteins for triiodothyronine. In contrast to the behaviour of the percentages of socalled free and protein bound triiodothyronine the absolute amount of protein bound triiodothyronine was rising linearly with rising concentrations of triiodothyronine added. The curve obtained was interpreted as resulting from saturation curves of different triiodothyronine binding proteins and discharge curves of competitively bound substances, e.g. thyroxine.3. Dextran gel is not acting merely as molecular sieve for triiodothyronine, but rather competing actively with serum proteins for triiodothyronine, adsorbing the latter. The physiological rôle of the socalled free triiodothyronine is discussed.4. With addition of l-thyroxine-131I 80% of131iodine was recovered, when the method ofBarker for determination of serum protein bound127iodine (open alkaline ashing) was used.
Mit Unterstützung der Deutschen Forschungsgemeinschaft.
Herrn Prof. Dr. Dr. h. c.Carl Krauspe in Verehrung zum 70. Geburtstag gewidmet. 相似文献
7.
The 39-kilodalton protein of Borrelia burgdorferi: a target for bactericidal human monoclonal antibodies. 总被引:3,自引:6,他引:3
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Three human monoclonal immunoglobulin M antibodies against Borrelia burgdorferi, obtained from in vitro-stimulated peripheral blood lymphocytes, reacted in Western blots (immunoblots) with a prominent 39-kDa peptide and a faint band of approximately 66 kDa. Two of these antibodies showed bactericidal activity without addition of complement. All three antibodies were reactive in an enzyme immunoassay with cloned P39 (W.J. Simpson, M.E. Schrumpf, and T.G. Schwan, J. Clin. Microbiol. 28:1329-1337, 1990), suggesting that the target molecule of these antibodies is identical to the P39 protein. In addition, the majority of supernatants from human lymphocytes stimulated in vitro with crude B. burgdorferi antigen reacted in this assay, demonstrating that P39, although a minor component of B. burgdorferi, is an immunodominant antigen in these spirochetes. A fourth monoclonal antibody, reacting with OspA, also exhibited bactericidal activity. 相似文献
8.
K. Horn G. Brehm J. Habermann C. R. Pickardt P. C. Scriba 《Journal of molecular medicine (Berlin, Germany)》1976,54(20):983-986
Zusammenfassung Bei einem 26jährigen Patienten im thyreotoxischen Koma erwies sich die kontinuierliche Plasmapherese am IBM-Blutzellseparator klinisch als akut wirksame Krisentherapie. Schon während der Plasmapherese mit Austausch von 51 Plasma in 3 1/2 h wurde der Patient aus einem tiefen Koma heraus ansprechbar. Mit den 51 Plasma wurden 633 µg Thyroxin (T4) und 13,6 µg Trijodthyronin (T3) entzogen. Dies führte erstaunlicherweise nicht zu einem Abfall der Gesamtspiegel von T4 und T3 im Serum, ein Befund, der als Hinweis auf einen raschen Rückstrom aus dem Gewebe in die Blutbahn zu interpretieren ist. Die freien Schilddrüsenhormonspiegel nahmen dagegen signifikant ab, erkennbar am Abfall der Werte des T3-in vitro-Tests und der T4- und T3-Ausscheidung im Urin. Diese Befunde zeigen auf, daß neben dem Entzug von Schilddrüsenhormon vor allem die Zufuhr freier Bindungsstellen für Schilddrüsenhormon mit dem Spenderplasma bei der Behandlung der thyreotoxischen Krise von Bedeutung ist.Mit Unterstützung der Sonderforschungsbereiche SFB 511 und SFB 372 相似文献
9.
The pathogenesis of herpes simplex virus types 1 and 2 has been studied in guinea pigs after inoculation by various routes (subcutaneous and intradermal infection in footpads and vaginal infection). Clinical observations as well as virus isolation studies are reported. Herpes simplex virus type 2 infection by all three routes of inoculation led to acute primary and recurrent lesions. Virus persisted in the nervous system, particularly in sensory ganglia, and locally at the site of inoculation. Herpes simplex virus type 1 infection induced no or very mild primary symptoms. Recurrent lesions were only observed after intradermal inoculation. Invasion of the nervous system and consequent establishment of latent ganglionic infection was less efficient than after herpes simplex virus type 2 infection. Peripheral persistence was, however, equally common. 相似文献
10.
Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family 总被引:3,自引:0,他引:3
Fagerheim T; Nilssen O; Raeymaekers P; Brox V; Moum T; Elverland HH; Teig E; Omland HH; Fostad GK; Tranebjaerg L 《Human molecular genetics》1996,5(8):1187-1191
Hereditary hearing impairment affects about 1 in 1000 newborns. In most
cases hearing loss is non-syndromic with no other clinical features, while
in other families deafness is associated with specific clinical
abnormalities. Analysis of large families with non-syndromic and syndromic
deafness have been used to identify genes or gene locations that cause
hearing impairment. The present report describes a large Norwegian family
with autosomal dominant non-syndromic, progressive high tone hearing loss
with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was
obtained with the microsatellite marker D1S196. Analysis of recombinant
individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104
and D1S466. The region contains several attractive candidate genes. This
report supports the idea of extensive genetic heterogeneity in hereditary
hearing impairment and represents the first localization of a deafness gene
in a Norwegian family.
相似文献