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31.
Juha Juntunen Juhani Huuskonen Krista Laine Riku Niemi Hannu Taipale Tapio Nevalainen David W Pate Tomi J?rvinen 《European journal of pharmaceutical sciences》2003,19(1):37-43
Phosphate esters of arachidonylethanolamide (AEA) and R-methanandamide were synthesized and evaluated as water-soluble prodrugs. Various physicochemical properties (pK(a), partition coefficient, aqueous solubility) were determined for the synthesized phosphate esters. The chemical stability of phosphate esters was determined at pH 7.4. In vitro enzymatic hydrolysis rates were determined in 10% liver homogenate, and in a pure enzyme-containing (alkaline phosphatase) solution at pH 7.4. The intraocular pressure (IOP) lowering properties of R-methanandamide phosphate ester were tested on normotensive rabbits. The phosphate promoiety increased the aqueous solubility of the parent compounds by more than 16500-fold at pH 7.4. Phosphate esters were stable in buffer solutions, but rapidly hydrolyzed to their parent compounds in alkaline phosphatase solution (t(1/2)<15 s) and liver homogenate (t(1/2)=8-9 min). The phosphate ester of R-methanandamide reduced IOP in rabbits. These results indicate that the phosphate esters of AEA and R-methanandamide are useful water-soluble prodrugs. 相似文献
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Levodopa, bromocriptine and selegiline modify cardiovascular responses in Parkinson's disease 总被引:2,自引:0,他引:2
Haapaniemi TH Kallio MA Korpelainen JT Suominen K Tolonen U Sotaniemi KA Myllylä VV 《Journal of neurology》2000,247(11):868-874
Autonomic nervous system (ANS) involvement is frequently found in Parkinson's disease (PD), but its causal relationship to
the disease itself and its medication is unclear. We evaluated the effects of PD medications on cardiovascular ANS functions.
Heart rate (HR) responses to normal and deep breathing, the Valsalva manoeuvre and tilting, and blood pressure (BP) responses
to tilting and isometric work were measured prospectively in 60 untreated PD patients randomised to receive either levodopa
(n=20), bromocriptine (n=20) or selegiline (n=20) as their initial treatment. The results were compared with those of 28 healthy controls. The responses were recorded
at baseline, after 6 months on medication and following a 6-week washout period. At baseline HR responses to normal breathing,
deep breathing and tilting were already lower and the fall in the systolic BP immediately and at 5 min after tilting was more
pronounced in the PD patients than in the controls. Six months' levodopa treatment diminished the systolic BP fall after tilting
when compared to baseline, whereas bromocriptine and selegiline increased the fall in systolic BP after tilting and selegiline
diminished the BP responses to isometric work. The BP responses returned to the baseline values during the washout period.
The drugs induced no change in the HR responses. Thus PD itself causes autonomic dysfunction leading to abnormalities in HR
and BP regulation and the PD medications seem to modify ANS responses further. Bromocriptine and selegiline, in contrast to
levodopa, increase the orthostatic BP fall and supress the BP response to isometric exercise reflecting mainly impairment
of the sympathetic regulation.
Received: 17 February 2000 / Received in revised form: 25 May 2000 / Accepted: 15 June 2000 相似文献
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Reference Values for Echocardiography in Middle‐Aged Population: The Cardiovascular Risk in Young Finns Study 下载免费PDF全文
Saku Ruohonen Ph.D Juha W. Koskenvuo M.D. Ph.D. Maria Wendelin‐Saarenhovi M.D. Ph.D. Mikko Savontaus M.D. Ph.D. Mika Kähönen M.D. Ph.D. Tomi Laitinen M.D. Ph.D. Terho Lehtimäki M.D. Ph.D. Eero Jokinen M.D. Ph.D. Jorma Viikari M.D. Ph.D. Markus Juonala M.D. Ph.D. Leena Taittonen M.D. Ph.D. Päivi Tossavainen M.D. Ph.D. Merja Kallio M.D. Ph.D. Jeroen J. Bax M.D. Ph.D. Olli Raitakari M.D. Ph.D. 《Echocardiography (Mount Kisco, N.Y.)》2016,33(2):193-206
37.
Short DNA sequences and bacterial DNA induce esophageal,gastric, and colorectal cancer cell invasion
Joonas H. Kauppila Tuomo J. Karttunen Juha Saarnio Pia Nyberg Tuula Salo David E. Graves Katri S. Selander 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2013,121(6):511-522
Toll‐like receptor 9 (TLR9) recognizes both bacterial and self‐DNA and it is abundantly expressed in the gastrointestinal tract. In this study, we investigated the influences of both bacterial DNA and specific short DNA sequences on TLR9‐mediated gastrointestinal cancer cell invasion. We assessed the effect of various DNA ligands on cellular invasion and on TLR9 and matrix metalloproteinase expression of three gastrointestinal cancer cell lines. DNA‐ligands described in this study include CpG‐ODN M362, 9‐mer (hairpin), human telomeric sequence h‐Tel22 G‐quadruplex, and bacterial DNAs from Escherichia coli and Helicobacter pylori. All of the DNAs studied were demonstrated to induce invasion in the studied cells. The DNA‐induced invasion was inhibited with a broad‐spectrum MMP inhibitor and partly also with chloroquine suggesting that it could be mediated via MMP activation, endosomal signaling, and TLR9. Interestingly, H. pylori DNA was shown to induce a more pronounced invasion in a gastric cancer cell line than in the other cell lines. Our results suggest that bacterial DNA as well as deoxynucleotides having stable secondary structures (i.e. hairpins or G‐quadruplex structures) may serve as endogenous, invasion‐inducing TLR9‐ligands and promote local progression and metastasis of cancers in the alimentary tract. 相似文献
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Eetu Heervä Laura Huilaja Pekka Leinonen Sirkku Peltonen Juha Peltonen 《Calcified tissue international》2014,94(6):608-612
This is the first prospective follow-up study to describe the effects of oral alendronate medication on neurofibromatosis 1 (NF1)-related osteoporosis. NF1 is a neurocutaneous skeletal syndrome associated with increased fracture risk and high frequency of osteopenia and osteoporosis. Alendronate is a bisphosphonate drug which inhibits the function of bone-resorbing osteoclasts, ultimately leading to an increase in bone mineral density (BMD) and reduction in fracture risk. However, in vitro studies have shown that NF1 osteoclasts display insensitivity to apoptotic signals caused by bisphosphonates. Our aim was to monitor the effects of alendronate medication in patients with NF1. Five men and one woman, aged 28–76 years, with NF1-related osteoporosis were enrolled to the study. Study participants did not have other conditions and were not taking any medication known to affect bone. The medication included a weekly dose of 70 mg alendronate and a daily 20 μg vitamin D supplementation. After 23 months of follow-up, BMD was increased in five out of six patients, but the increase was not statistically significant. Serum levels of the bone turnover markers CTX and PINP were reduced, suggesting slower bone remodeling, as expected. An unexpected result was that serum levels of the osteoclast activity marker TRAP5b did not change during the follow-up. One new stress fracture of the tibia was documented during the alendronate therapy. Even though the study group was small, the findings of the current study (one new fracture and one patient with decreased BMD) call for a larger study to assess the efficacy of bisphosphonates in NF1-related osteoporosis. 相似文献