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101.
102.
Methanol is a widely used solvent and a potential fuel for motor vehicles. Human kinetic data of methanol are sparse. As a basis for biological exposure monitoring and risk assessment, we studied the inhalation toxicokinetics of methanol vapor in four female and four male human volunteers during light physical exercise (50 W) in an exposure chamber. The relative uptake of methanol was about 50% (range 47-53%). Methanol in blood increased from a background level of about 20 to 116 and 244 microM after 2 h exposure at 0, 100 ppm (131 mg/m3) and 200 ppm (262 mg/m3), respectively. Saliva showed substantially higher levels than blood immediately after exposure. This difference disappeared in a few minutes; thereafter the concentrations and time courses in blood, urine, and saliva were similar, with half times of 1.4, 1.7, and 1.3 h, respectively. The postexposure decrease of methanol in exhaled air was faster, with a half time of 0.8 h. The methanol concentrations were approximately twice as high in all four types of biological samples at 200 compared to 100 ppm. No increase in urinary formic acid was seen in exposed subjects. Our study indicates non-saturated, dose-proportional kinetics of methanol up to 200 ppm for 2 h. No gender differences were detected. Similar, parallel patterns were seen with regard to the methanol time courses in blood, urine, and saliva, whereas the concentration in exhaled air decreased markedly faster. Thus, apart from blood and urine, saliva also seems suitable for biomonitoring of methanol exposure. 相似文献
103.
Shinichiro Asakawa Shigeyuki Arai Mika Kawagoe Chiaki Ohata Wataru Ono Hiroshi Murata Yoshifuru Tamura Shunya Uchida Shigeru Shibata Yoshihide Fujigaki 《Internal medicine (Tokyo, Japan)》2022,61(9):1423
A young woman with microscopic polyangiitis (MPA) requiring hemodialysis showed repeated posterior reversible encephalopathy syndrome (PRES) with spatiotemporal multiple lesions over a period of two months. The first PRES episode with confusion and the second PRES episode with vertigo and nausea were caused by MPA, hypertension and renal failure. These symptoms were improved by the reinforcement of MPA treatment and blood pressure management. The third PRES episode with nausea, headache, seizure and visual changes was induced by rituximab infusion and hypertension. The PRES was improved with blood pressure and convulsant management. These conditions are challenging to diagnose and treat. 相似文献
104.
Norio Imai Mayumi Kawabe Seiko Tamano Yuko Doi Hironao Nakashima Mayuko Suguro Takamasa Numano Tomomi Hara Akihiro Hagiwara Fumio Furukawa Yoshihisa Kaneda Norifumi Tateishi Wataru Fujii Hiroshi Kawashima Hiroshi Shibata Yutaka Sakakibara 《Food and chemical toxicology》2012
The modifying potential on tumor development of arachidonate-enriched triglyceride oil (ARA-oil) containing approximately 40% arachidonic acid was investigated in a medium-term multi-organ carcinogenesis bioassay using male and female F344 rats. The animals were sequentially given five carcinogens with different target sites in the first 4 weeks, and then administered ARA-oil for 24 weeks at dietary levels of 0% (control), 1.25%, 2.5% or 5.0%. No statistically significant differences in incidences and multiplicities of hyperplastic and neoplastic lesions were showed in the large intestine in either sex. In the liver, kidney, and lung in both sexes, and the mammary gland and uterus in females, tumor promoting potential was not evident with ARA-oil treatment. ARA-oil did not affect the quantitative data for glutathione S-transferase placental form positive foci of the liver. Increased induction of hyperplastic or neoplastic lesions in the urinary bladder and thyroid in ARA-oil-treated groups was without dose dependence. In addition, a second experiment with ARA-oil only administration for 8-week revealed no effects on cellular proliferation in the urinary bladder or thyroid in either sex. These results indicate that ARA-oil has no tumor promoting potential in any organs or tissues initiated with the five carcinogens applied in the present study. 相似文献
105.
M A Shibata A Hagiwara S Tamano S Ono S Fukushima 《Journal of toxicology and environmental health》1989,26(3):255-265
The effect of the diuretic drug furosemide on two-stage urinary bladder carcinogenesis in F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated with regard to possible promoting activity. BBN was administered at 2 doses, 0.01 or 0.05%, in drinking water for 4 wk, and thereafter furosemide was given by gavage 3 times weekly for 32 wk, 250 mg/kg body weight. Furosemide ingestion induced diuresis with an alkaline, hypotonic urine. No significant difference with regard to incidences of bladder lesions were apparent between furosemide and control groups. The present investigation indicated that neither furosemide nor its related polyuria acted as a promoter in two-stage urinary bladder carcinogenesis. 相似文献
106.
T Shibata M Nishikawa Y Tsurumi S Takase H Terano M Kohsaka 《The Journal of antibiotics》1989,42(9):1356-1361
FR-901235 is a new type of immunoactive substance produced by an imperfect fungus, Paecilomyces carneus F-4882. The mitogen-induced lymphocyte proliferation which had been suppressed by addition of immunosuppressive factor, was restored to a normal level by the addition of FR-901235. Furthermore, the subsequent administration of FR-901235 partially restored the impaired delayed-type hypersensitivity to sheep red blood cells in tumor-bearing mice. 相似文献
107.
Fukami H Imajo S Ito A Kakutani S Shibata H Sumida M Tanaka T Niwata S Saitoh M Kiso Y Miyazaki M Okunishi H Urata H Arakawa K 《Drug design and discovery》2000,17(1):69-84
A series of 3-phenylsulfonylquinazoline-2,4-dione derivatives have been synthesized and evaluated for their ability to inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The phenyl moiety of quinazoline participates in a hydrophobic interaction where an optimum size is required. In this moiety, 7-chloroquinazoline is the best moiety for inhibiting chymase, chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrophobic electron-withdrawing groups at the 4-position potentiated the activity. Anthranil moiety also enhanced the activity. Pyridylmethyl and N-pyridylacetamide at the 1-position gave an IC50 in the order of 10(-8)M. Molecular modeling studies on the interaction of 7-chloro-3-(4-chlorophenylsulfonyl) quinazoline-2,4(1H, 3H)-dione (4) with the active site of human heart chymase suggested that the phenyl moiety of quinazoline interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, the moiety at the 1-position locates in the S2-S3 subsites and the 4-carbonyl and 3-sulfonyl group interact with the oxyanion hole and the His57 side-chain of chymase, respectively. 相似文献
108.
Mao Hagihara Hideo Kato Toshie Sugano Hayato Okade Nobuo Sato Yuichi Shibata Daisuke Sakanashi Nobuhiro Asai Yusuke Koizumi Hiroyuki Suematsu Yuka Yamagishi Hiroshige Mikamo 《International journal of antimicrobial agents》2021,57(5):106330
BackgroundCarbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) are difficult to treat and are a serious public health threat. Nacubactam (NAC) is a novel non-β-lactam diazabicyclooctane β-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of β-lactamases.MethodsThe antimicrobial efficacy of meropenem (MEM), cefepime (FEP), and aztreonam (ATM), each in combination with NAC, were assessed in vitro and in vivo against Klebsiella pneumoniae and Escherichia coli. Ten isolates, including CRE and/or CPE with β-lactamase genes, were used in this study. The relationship between phenotype and in vivo efficacy was assessed in a murine neutropenic thigh-infection model. Efficacy was determined by the change in bacterial quantity.ResultsThe results of the in vitro study showed the minimum inhibitory concentrations of the combination of NAC with either MEM, FEP, or ATM in a 1:1 ratio were 2 to >128-fold lower than those of MEM, FEP, or ATM alone against CRE+ isolates. In addition, combinations of β-lactams and NAC administered in the murine thigh-infection model showed greater efficacy against CRE+/CPE+, CRE+/CPE-, and CRE-/CPE+ isolates harboring various β-lactamase genes (IMP-1, IMP-6, KPC, DHA-1, or OXA-48) compared with MEM, FEP, ATM, and NAC alone.ConclusionMEM, FEP, or ATM in combination with NAC showed potent in vivo antimicrobial activity in a murine thigh-infection model caused by K. pneumoniae and E. coli, including CRE and/or CPE isolates. These findings indicate that these combinations of β-lactams and NAC are potential candidates for the treatment of CRE and/or CPE infections. 相似文献
109.
Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice 总被引:1,自引:0,他引:1
S Shibata H Inoue S Iwata R D Ma L J Yu H Ueyama J Takayasu T Hasegawa H Tokuda A Nishino 《Planta medica》1991,57(3):221-224
Licochalcone A, 3-a,a-dimethylallyl-4,4'-dihydroxy-6-methoxychalcone, from the root of Glycyrrhiza inflata Beta (Leguminosae) (Xin-jiang liquorice) showed anti-inflammatory action towards mouse ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol 13-acetate (TPA) by topical application. Anti-tumour promoting action of licochalcone A was also observed in vivo for mouse skin papilloma initiated by dimethylbenz[a]anthracene (DMBA) and promoted by TPA. It inhibited in vitro 32Pi-incorporation to phospholipids in HeLa cells promoted by TPA. A competitive interaction of licochalcone A with the TPA-receptors in the cell membrane has been suggested. 相似文献
110.
A. Sasaki F. Tanaka K. Mimori H. Inoue S. Kai K. Shibata M. Ohta S. Kitano M. Mori 《European journal of surgical oncology》2008