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101.
Metabolism and excretion of atorvastatin in rats and dogs. 总被引:1,自引:0,他引:1
Atorvastatin (AT) is a second-generation potent inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, clinically approved for lowering plasma cholesterol. Using a mixture of [D(5)/D(0)] AT and/or [(14)C]AT, the metabolic fate and excretion of AT were examined in rats and dogs following single and multiple oral doses. Limited biliary recycling was examined in one dog after a single dose of AT. AT-derived metabolites in bile samples were identified by metabolite screening of the [D(5)/D(0)] AT molecular clusters using tandem mass spectrometry. Bile was a major route of [(14)C] drug-derived excretion, accounting for 73 and 33% of the oral dose in the rat and dog, respectively. The remaining radioactivity was recovered in the feces; only trace amounts were excreted in urine. Radioactive components identified in rat and dog bile were the para- and ortho-hydroxy metabolites, a glucuronide conjugate of ortho-hydroxy AT, and unchanged AT. Two minor radioactive components were identified as beta-oxidation products of AT with one confirmed as a beta-oxidized AT derivative. The reappearance of AT and major metabolites in bile from a dog administered a sample of its previously excreted bile indicated biliary recycling is an important component in AT metabolism. Multiple dose administration in rats did not alter biliary metabolic profiles. Rat and dog plasma profiles after multiple dose administration were similar and showed no additional metabolites not found in bile. Examination of rat and dog bile and plasma indicates that AT primarily undergoes oxidative metabolism. 相似文献
102.
Lim YH Leem MJ Shin DH Chang HB Hong SW Moon EY Lee DK Yoon SJ Woo WS 《Archives of pharmacal research》1999,22(2):208-212
Activity-guided fractionation of the roots of Anthriscus sylvestris resulted in the isolation and characterization of five cytotoxic compounds, deoxypodophyllotoxin (1), falcarindiol (2), and angeloyl podophyllotoxin (5) from the hexane soluble fraction and morelensin (3), bursehernin (4) from the chloroform soluble fraction. It is the first report of the occurrence of compound 5 in nature. 相似文献
103.
2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor activity (T/C, 125 to approximately 218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s). 相似文献
104.
Optimum conditions of chiral derivatization reaction of beta-blockers acebutolol, arotinolol, beta-xolol, bisoprolol, celiprolol, metoprolol and pindolol) with (-)-menthyl chloroformate were investigated for the resolution by HPLC. With more than 30 times molar excess of (-)-menthyl chloroformate chiral derivatization reactions were completed within one hour at room temperature except arotinolol and celiprolol. Diastereomeric derivatives of beta-blockers were well resolved on the ODS column using acetonitrile-methanol-water as a mobile phase. 相似文献
105.
Yong -Hyun Kim Do -Youn Won Chang -Young Oh Nam -Tae Woo Young -Ho Park Jin -Hyun Jeong Won -Hun Ham 《Archives of pharmacal research》1999,22(3):300-301
Stereoselective synthesis of (+/-)-epibatidine analog 2, which contains the 8-azabicyclo[3.2.1]octane ring system, was achieved by using palladium-catalyzed Heck-type coupling reaction from 3. 相似文献
106.
Hak Cheol Kwon Byeong Gon Lee Seung Hee Kim Chil Mann Jung Sung Youl Hong Jeung Whan Han Hyang Woo Lee Ok Pyo Zee Kang Ro Lee 《Archives of pharmacal research》1999,22(4):410-413
In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells. 相似文献
107.
Cytotoxicity of urushiols isolated from sap of Korean lacquer tree (Rhus vernicifera stokes) 总被引:1,自引:0,他引:1
Hong DH Han SB Lee CW Park SH Jeon YJ Kim MJ Kwak SS Kim HM 《Archives of pharmacal research》1999,22(6):638-641
Cytotoxicities of four urushiols, congeners isolated from the sap of Korean lacquer tree (Rhus vernicifera Stokes), to 29 human cancer cell lines originated from 9 organs were evaluated. Their values of 50% growth inhibition were below 4 microg/ml, and showed cell line specific cytotoxicity. The present result is the first report on the cytotoxicity of urushiols suggesting that they would have an anticancer activity to human cancer cells. 相似文献
108.
E. Y. Liang W. W. M. Lam J. K. S. Woo C. A. van Hasselt C. Metreweli 《European radiology》1996,6(4):553-556
In order to study the features of sinonasal polyposis (SNP) on CT, 100 consecutive coronasal sinus CT examinations done for chronic inflamamtory sinonasal disease were reviewed. The CT findings of the 27 fully documented SNPs were analyzed. All our SNPs were bilateral. There was a strong tendency for extensive involvement. Nasal polyps were seen in 22 of 27 (81%); bony trabecular deossification in 23 of 27 (85%); widening of infundibulum in 26 of 27(96%). We discovered a new sign truncation of the bony middle turbinate, where the bulbous part of bony middle turbinate was missing, in 51 of 26 (58 %) of SNP patients without a previous history of middle turbinectomy, 12 of 15(80%) were bilateral. The one SNP patient (1 of 27) with previous middle turbinectomy was not regarded to be real truncation. Truncation of the bony middle turbinate is a characteristic and easily recognizable ancillary sign, and is not seen in other patterns of sinusitis. Together with other features on coronal sinus CT, this adds diagnostic confidence in diagnosing sinonasal polyposis.
Correspondence to: E. Y. Liang 相似文献
109.
The Gastric Bypass for Failed Bariatric Surgical Procedures 总被引:1,自引:0,他引:1
Background: Revision of failed bariatric surgical procedures is a significant challenge for every bariatric surgeon. Methods:
Evaluated are surgical difficulties, management problems and weight loss in patients with distal gastric bypass as a revisionary
procedure. Eighty patients were followed up to 3 years; four were lost to follow-up. Mean age was 43; mean prebariatric surgery
weight 134 kg; height 1.65 meters; body mass index 40.1; ideal body weight 62.7 kg; excess weight 70.5 kg; per cent excess
weight 214%. A 250 cm stomach-to-ileocecal valve segment of small bowel was used, and the biopancreatic secretions were brought
into the terminal ileum 100 cm from the ileocecal valve. Mean pouch size was 63 cc; length of hospital stay 5 days; operative
blood loss 616 cc; operative time 130 min. Results: Intraoperative complications included three splenic injuries (without
splenectomy). Early complications included one deep vein thrombosis, two marginal ulcers, one GI hemorrhage, one wound dehiscence,
one pouch outlet obstruction and one pancreatitis. Late complications included: one death from protein malnutrition/ARDS;
21 hypoproteinemia; six protein malnutrition, and of these, three had hyperalimentation; three cholecystitis; 27 anemia; 22
incisional hernia; two staple-line disruption (reoperated); 26 low serum iron; 11 prolonged (> 6 months) diarrhea; three prolonged
frequent vomiting; and two unrelated deaths (chronic myelogenous leukemia and amyotrophic lateral sclerosis). Mean excess
weight loss was 83% at 12 months; 89% at 24 months; and 94% at 36 months. Conclusion: The distal gastric bypass is fraught
with the operative and immediate post-operative complications experienced in any revisionary bariatric surgery. Distal gastric
bypass is very effective in producing long-term weight loss. Nutritional problems are common but usually easily corrected.
The most serious nutritional complication is protein malnutrition, which must be identified and corrected early. Success of
this procedure is dependent upon patient compliance with proper nutrition and supplements, and regular office follow-up with
monitoring of laboratory data. Patients who are noncompliant are at significant risk for complications. 相似文献
110.
Relation between genotype and phenotype in Swedish phenylketonuria and hyperphenylalaninemia patients 总被引:6,自引:0,他引:6
E. Svensson U. von Döbeln R. C. Eisensmith L. Hagenfeldt S. L. C. Woo 《European journal of pediatrics》1993,152(2):132-139
Phenylketonuria (PKU) and hyperphenylalaninemia (HPA) are caused mostly by an inherited (autosomal recessive) deficiency in hepatic phenylalanine hydroxylase (PAH) activity. More than 50 PAH mutations have ben reported. The goal of the present study was to examine the molecular basis for the clinical heterogeneity of Swedish PKU and HPA patients. Mutations were identified through allele-specific oligonucleotide hybridization or DNA sequencing on 128 of the 176 mutant alleles (73%). Three mutations (R408W, Y414C and IVS12) together accounted for 56% of all mutant alleles and ten relatively infrequent mutations were found on another 17% of all mutant alleles. Patients from 50 of the 88 families (57%) had identified mutations in both PAH genes and allowed use to compare the clinical effects of different combinations of PAH mutations. The in vitro activity of all of these mutations, including the newly identified G272X and L364, have been tested in a eukaryotic expression system. There was a strong relationship between the average in vitro PAH activity of the two mutant enzymes and both the phenylalanine tolerance and the neonatal pretreatment serum phenylalanine concentration. This confirms previous observations in Danish and German PKU patients that disease phenotype is a consequence of the nature of the mutations at the PAH locus and not significantly influenced by other loci. The sample population in the previous study did not, however, include mild HPA patients, and the observed correlation is thus restricted to severe and moderate mutant alleles. Since a comparatively high proportion of the Swedish patients were mildly affected, we have provided additional evidence that this correlation is valid throughout a continuous spectrum of clinical varieties. PAH genotyping could therefore help predict prognosis of a recently diagnosed PKU or HPA child. 相似文献