全文获取类型
收费全文 | 140404篇 |
免费 | 12850篇 |
国内免费 | 3932篇 |
专业分类
耳鼻咽喉 | 896篇 |
儿科学 | 3315篇 |
妇产科学 | 2212篇 |
基础医学 | 24524篇 |
口腔科学 | 3210篇 |
临床医学 | 8800篇 |
内科学 | 23619篇 |
皮肤病学 | 2422篇 |
神经病学 | 14103篇 |
特种医学 | 3897篇 |
外国民族医学 | 29篇 |
外科学 | 13178篇 |
综合类 | 12528篇 |
现状与发展 | 17篇 |
预防医学 | 6940篇 |
眼科学 | 1382篇 |
药学 | 19794篇 |
40篇 | |
中国医学 | 4726篇 |
肿瘤学 | 11554篇 |
出版年
2023年 | 2274篇 |
2022年 | 5179篇 |
2021年 | 6100篇 |
2020年 | 5037篇 |
2019年 | 6305篇 |
2018年 | 6049篇 |
2017年 | 5344篇 |
2016年 | 4726篇 |
2015年 | 5279篇 |
2014年 | 7866篇 |
2013年 | 8183篇 |
2012年 | 6925篇 |
2011年 | 8119篇 |
2010年 | 6549篇 |
2009年 | 6632篇 |
2008年 | 6452篇 |
2007年 | 5538篇 |
2006年 | 4863篇 |
2005年 | 4390篇 |
2004年 | 3753篇 |
2003年 | 3427篇 |
2002年 | 2535篇 |
2001年 | 2201篇 |
2000年 | 1890篇 |
1999年 | 1782篇 |
1998年 | 1632篇 |
1997年 | 1569篇 |
1996年 | 1418篇 |
1995年 | 1278篇 |
1994年 | 1176篇 |
1993年 | 1081篇 |
1992年 | 854篇 |
1991年 | 784篇 |
1990年 | 664篇 |
1989年 | 580篇 |
1988年 | 557篇 |
1986年 | 624篇 |
1985年 | 1728篇 |
1984年 | 2451篇 |
1983年 | 1640篇 |
1982年 | 1743篇 |
1981年 | 1634篇 |
1980年 | 1398篇 |
1979年 | 1218篇 |
1978年 | 1008篇 |
1977年 | 856篇 |
1976年 | 969篇 |
1975年 | 663篇 |
1974年 | 577篇 |
1973年 | 618篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
921.
The capacity of N-oxidized metabolites of 4,4-methylenebis(2-chloroaniline) (MBOCA) to form hemoglobin (Hb) adducts was determined in vitro, and the formation of Hb adducts following in vivo administration of MBOCA was assessed with or without prior induction of cytochrome P-450 enzymes with phenobarbital or -naphthoflavone. Hb adduct formation was determined by electron-capture GLC of MBOCA as the heptafluorobutyryl derivative following mild acid hydrolysis of protein-bound MBOCA. The method was confirmed by gas chromatography-mass spectrometry with selected ion monitoring. N-hydroxy- and mononitroso-MBOCA, but not MBOCA itself, formed adducts to rat and human Hb in vitro in a dose-related manner. Binding was inhibited by cysteine and glutathione but not oxidized glutathione or methionine. Intravenous administration of as little as 0.04 mol/kg N-hydroxy-MBOCA to rats resulted in measurable formation of MBOCA-Hb adducts (0.9 ng/50 mg Hb). Intraperitoneal administration of 0.5–50 mg/kg MBOCA to rats, and subcutaneous administration of 5–500 mg/kg MBOCA to rats and 4–100 mg/kg to guinea pigs resulted in dose-related formation of Hb adducts. MBOCA-Hb remained elevated in blood for greater than 10 weeks following a single subcutaneous dose in guinea pigs. Pretreatment of rats with phenobarbital induced microsomal benzphetamine N-demethylase (BND) activity and resulted in a small increase in in vitro N- andortho- hydroxylation of MBOCA, but did not increase in vivo Hb adducts. Pretreatment of rats with -naphthoflavone induced microsomal aryl hydrocarbon hydroxylase as well as ethoxyresorufin-O-deethylase, and increased in vitro N- but notortho-hydroxylation of MBOCA. -Naphthoflavone pretreatment increased the formation of MBOCA-Hb adducts when rats were dosed with MBOCA at 100 and 500 mg/kg, but not 20 mg/kg subcutaneously. 相似文献
922.
Interactions of halogenated industrial chemicals with transthyretin and effects on thyroid hormone levels in vivo 总被引:2,自引:0,他引:2
Van den Berg K. J. van Raaij J. A. G. M. Bragt P. C. Notten W. R. F. 《Archives of toxicology》1991,65(1):15-19
Previous results in experimental systems have suggested that hydroxylated PCBs may decrease thyroid hormone levels through associative interaction with transthyretin. In the present paper it was investigated whether this property was also shared by various industrial chemicals, mainly pesticides. In total, 65 compounds from 12 chemical groups were analyzed for direct interference with the T4 binding site of transthyretin using a competitive binding assay. Sixty per cent of the compounds were competitive at a concentration level of 100 M. Relatively strong interactions were observed by several chlorophenols, chlorophenoxy acids and nitrophenols, as well as by individual compounds such as hexachlorobenzene, dicofol, bromoxynil and tetrachlorohydroquinone. Examples from these chemical groups, e.g. pentachlorophenol, 2,4-dichlorophenoxybutyric acid, dinoseb and bromoxynil, also reduced plasma TT4 levels in rats. In addition, bromoxynil decreased plasma TT3 levels. The results suggest the existence of a number of halogenated industrial chemicals with a potential for lowering plasma thyroid hormone levels through interference with hormone transport carriers. 相似文献
923.
David A. Cheresh 《Cancer metastasis reviews》1991,10(1):3-10
Summary Human melanoma represents one of the most metastatic cancers in man. The capacity of melanoma cells to invade a variety of tissues and extracellular matrices is, in part, due to their repertoire of adhesion receptors. To this end, human melanoma cells express multiple integrin cell adhesion receptors among these is the vitronectin receptor, v3. This adhesion receptor enables melanoma cells to attach to a wide variety of extracellular matrix components containing the sequence Arg-Gly-Asp. This review will focus on the biosynthetic, biochemical and biological properties of this receptor expressed on the surface of human melanoma cells. 相似文献
924.
925.
G. J. Molderings G. Weißenborn E. Schlicker J. Likungu M. Göthert 《Naunyn-Schmiedeberg's archives of pharmacology》1992,346(1):46-50
Summary The human saphenous vein was used to examine whether presynaptic histamine receptors can modulate noradrenaline release and, if so, to determine their pharmacological characteristics. Strips of this blood vessel were incubated with [3H]noradrenaline and subsequently superfused with physiological salt solution containing desipramine and corticosterone. Electrically (2 Hz) evoked 3H overflow was inhibited by histamine and the H3 receptor agonist R-(–)--methylhistamine. Histamine-induced inhibition of electrically evoked tritium overflow was not affected by 2-adrenoceptor blockade by rauwolscine. S-(+)--methylhistamine (up to 10 mol/l) as well as the histamine H1 and H2 receptor agonists 2-(2-thiazolyl)ethylamine (up to 3 mol/l) and dimaprit (up to 30 mol/l), respectively, were ineffective. The selective histamine H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine. The histamine H2 and H1 receptor antagonists ranitidine and pheniramine, respectively, did not affect the histamine-induced inhibition of evoked tritium overflow. The present results are compatible with the suggestion that the sympathetic nerves of the human saphenous vein are endowed with inhibitory presynaptic histamine receptors of the H3 class.
Send offprint requests to M. Gothert at the above address 相似文献
926.
Summary The effects of 5-methoxytryptamine and 5-hydroxytryptamine (5-HT) on both basal and electrically evoked outflow of tritium were studied in guinea-pig myenteric plexus preparations preincubated with [3H]-choline.
Basal outflow. 5-Methoxytryptamine caused a transient and calcium-dependent increase in basal outflow of [3H]acetylcholine that was abolished by tetrodotoxin. Ondansetron (1 mol/1) did not affect the stimulatory response of 5-methoxytryptamine but ICS 205-930 (1 and 3 mol/1) produced parallel rightward displacements of the concentration-response curve to 5-methoxytryptamine. The PKB value for ICS 205-930 was 6.6 suggesting an involvement of 5-HT4 receptors. 5-HT caused an increase in basal outflow of [3H]acetylcholine and a biphasic concentration-response curve was obtained. The maximal response of the first phase to 5-HT (release of 0.98% of tissue tritium) and the maximal response to 5-methoxytryptamine (0.94% of tissue tritium) were similar but 5-methoxytryptamine (-log EC50: 6.9) was less potent than 5-HT (-log EC50 of the high affinity component: 7.9). ICS 205-930 (0.01–1.0 mol/1) acted as a competitive antagonist against the low affinity component of the 5-HT concentration-response curve with a pA2 value of 8.0. It is concluded that stimulation of both 5-HT4 receptors (by 5-methoxytryptamine and submicromolar concentrations of 5-HT) and 5-HT3 receptors (by micromolar concentrations of 5-HT) causes a release of acetylcholine which in turn leads to smooth muscle contraction.
Electrically evoked outflow. This outflow of [3H]acetylcholine was concentration-dependently inhibited by both 5-methoxytryptamine and 5-HT. ICS 205-930 (1 mol/1) reinforced the inhibitory effect of 5-methoxytryptamine but not that of 5-HT. In the presence of methiothepine (0.1 mol/1) 5-methoxytryptamine enhanced the evoked outflow of [3H]acetylcholine, an effect which was attenuated by 3 mol/1 ICS 205-930. These results suggest that 5-methoxytryptamine may both inhibit (via 5-HT1 receptors) and facilitate (via 5-HT4 receptors) the evoked release of acetylcholine from guinea-pig myenteric neurones. The facilitatory action is unmasked when the 5-HT1 receptor is blocked by methiothepine.
Send offprint requests to H. Kilbinger at the above address 相似文献
927.
Summary Evidence for a general role of phospholipase D in signal transduction is accumulating. In the present study, the activity of the enzyme was investigated in heart tissue under basal conditions and after addition of phorbol esters or aluminum fluoride (AlF
inf4
sup–
; 10 mM NaF plus 10 M AlCl3). Atria of rats and chickens were incubated with [3H]-myristic acid in order to label preferentially phosphatidylcholine. Under basal conditions, the tissues generated choline and phosphatidic acid (PtdOH), the primary catalytic products of phospholipase D. When 0.5 or 2.0% ethanol was present, [3H]-phosphatidyl-ethanol (PETH) was rapidly formed at the expense of [3H]-PtdOH. This transphosphatidylation reaction is specific for phospholipase D activity. The basal formation of PETH was not inhibited by a Ca2+-free, EGTA-containing medium. - The phorbol ester 4-phorbol-12,13-dibutyrate (PDB), which is known to activate protein kinase C, enhanced the net formation of choline, whereas the inactive 4-phorbol-13-acetate (PAc) was ineffective. PDB (0.2 M), in contrast to PAc, also increased the formation of [3H]-PtdOH and, in the presence of ethanol, of [3H]-PETH. The PDB-evoked formation of PETH occurred again at the expense of PtdOH. Treshold and maximum effective concentrations of PDB were 10 nM and 0.2–0.6 M, respectively. The effects of PDB on either choline efflux and generation of PETH showed the same Cat+-dependency, i.e., both effects were blocked by a Ca2+-free, EGTA-containing medium, but not by a Ca2+-free medium without EGTA. In protein kinase C-deficient tissue which was prepared by pretreatment with 0.61 M PDB for 27 h, PDB failed to enhance the formation of PtdOH and PETH. - A1F4–, a known activator of G-proteins, increased not only the tissue content of inositol phosphates, but also markedly enhanced choline efflux and formation of [3H]-PtdOH and PETH. In conclusion, in mammalian and avian atria a high phospholipase D activity was found even under basal conditions. The enzyme was stimulated by protein kinase C and presumably by a G protein.Abbreviations IP
inositol phosphate
- DAG
diacylglycerol
- PL
phospholipase
- PtdOH
phosphatidic acid
- PETH
phosphatidylethanol
- PDB
4-phorbol-12,13-dibutyrate
- PAc
4-phorbol-13-acetate
- AlF
inf4
sup–
aluminum fluoride
- DMSO
dimethylsulfoxide
Correspondence to K. Löffelholz at the above address 相似文献
928.
Maria L. Anthony Kevin P. R. Gartland Christopher R. Beddell John C. Lindon Jeremy K. Nicholson 《Archives of toxicology》1992,66(8):525-537
The acute toxicological effects of the nephrotoxic antibiotic cephaloridine (CPH, 0–1500 mg/kg) in male Fischer 344 (F344) rats, have been investigated over 48 h using clinical chemistry, histopathology and proton nuclear magnetic resonance (1H NMR) spectroscopy of urine and plasma. High field (400 and 600 MHz)1H NMR urinalysis revealed increased excretion of lactic acid, acetoacetate, alanine, valine, lysine, glutamine and glutamate and a severe, time-dependent glycosuria. A major change observed in urine of CPH-treated animals was the dose-dependent increase in HB which may relate to altered energy metabolism. CPH also caused dose-dependent decreases in the urinary excretion of hippurate, allantoin and protein (conventional assay). This abnormal metabolic profile is consistent with a functional defect in the S1/S2 regions of the proximal tubule, and was confirmed by histologypost mortem. Functional changes observed included elevations in blood urea nitrogen (BUN) and urine flow rate (UFR) and dose-related decreases in urine osmolality. Spin-echo1H NMR spectroscopic analysis of lyophilised plasma, reconstituted with2H2O revealed an abnormal phase modulation of the methyl signal from free alanine and it is postulated that this is due to the release of transaminases from damaged tissue which via a reversible conversion to pyruvate, cause variable deuteration of alanine at the -CH position. This observation suggests that1H NMR spectral patterns are also dependent on the level of plasma transaminases and this may provide a novel indicator of tissue damage. 相似文献
929.
The crystal structure and nuclear magnetic resonance (NMR) spectra and assignments of celiprolol, N-[3-acetyl-4[3-[N-t-butylamino-2-hydroxypropoxy]phenyl]-N, N-diethylurea, are reported. Celiprolol crystallizes in the monoclinic space group, P2l/a, with a = 9.081(2), b = 13.800(4), and c = 17.471(5) Å and = 95.04(2)°. Structure was solved by direct methods; structure refinement to R of 0.058. Intermolecular hydrogen-bonding in the crystal is discussed. The 1H, 13C, and two-dimensional (2D) NMR spectra of the hydrochloride have been obtained and definitive signal assignments made. 相似文献
930.
M. Duran R. J. A. Wanders J. P. de Jager L. Dorland L. Bruinvis D. Ketting L. Ijlst F. J. van Sprang 《European journal of pediatrics》1991,150(3):190-195
Two siblings were found to be affected by longchain 3-hydroxyacyl-CoA dehydrogenase deficiency, one of which died suddenly and unexpectedly on the 3rd day of life suffering from extreme hypoketotic hypoglycaemia. The younger sibling started to have feeding problems, lowered consciousness, and liver dysfunction at the age of 5 months. Her urine contained large amounts of C6–C14 3-hydroxydicarboxylic acids and conjugated 3-hydroxyoctanoic acid, as verified by gas chromatography/mass spectrometry. Plasma long-chain acylcarnitine was increased. A clue to the diagnosis was given by the results of a phenylpropionic acid loading test. This revealed small, but significant amounts of conjugated 3-hydroxyphenylpropionic acid (phenylhydracrylic acid) in the patient's urine. Subsequently, the activity of long-chain 3-hydroxyacyl-CoA dehydrogenase was found to be deficient in cultured skin fibroblasts. Based on the findings obtained by a medium-chain triglyceride load, a diet enriched in this type of fat was prescribed. On this regimen the patient started to thrive, signs of cardiomyopathy disappeared, and her liver function normalized. 相似文献