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排序方式: 共有1366条查询结果,搜索用时 31 毫秒
1.
Kamil Kuca Kamil Musilek Daniel Jun Eugenie Nepovimova Ondrej Soukup Jan Korabecny 《Toxin reviews》2020,39(2):157-166
AbstractOxime K074 was formerly considered to be a lead structure for design of novel oximes for reactivation of tabun-inhibited acetylcholinesterase (AChE). In this study, we are summarizing its reactivation activity in case of other nerve agents (sarin, cyclosarin, VX and Russian VX) and pesticides (chlorpyrifos, methylchlorpyrifos and DDVP). For this purpose, standard in vitro method using rat brain homogenate was used. As resulted, oxime K074 was able to reactivate brain ChE (cholinesterases) inhibited by all used nerve agents and pesticides excluding cyclosarin-inhibited ChE. Only slight modification in structure of sarin (isopropyl moiety) and cyclosarin (cyclohexyl moiety) caused extraordinary differences in the reactivation of acetylcholinesterase inhibited by these nerve agents. Obtained molecular docking results suggest that the oxime K074 interacts very well with the inhibitors addressed in this work, and the data obtained by the QM/MM approach showed a good correlation with our experimental results of reactivation rate (%) by the oxime K074. 相似文献
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More than just crushing: a prospective pre‐post intervention study to reduce drug preparation errors in patients with feeding tubes 下载免费PDF全文
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The New Acetylcholinesterase Inhibitors PC‐37 and PC‐48 (7‐Methoxytacrine‐Donepezil‐Like Compounds): Characterization of Their Metabolites in Human Liver Microsomes,Pharmacokinetics and In Vivo Formation of the Major Metabolites in Rats 下载免费PDF全文
Jana Zdarova Karasova Martin Mzik Milos Hroch Jan Korabecny Eugenie Nepovimova Viktor Vorisek Vladimir Palicka Kamil Kuca 《Basic & clinical pharmacology & toxicology》2018,122(4):373-382
The objective of this study was to elucidate the pharmacokinetics and metabolite formation of newly developed non‐selective AChE/BChE 7‐MEOTA‐donepezil‐like inhibitors for potential therapeutic use in Alzheimer's disease (AD) patients. The chemical structures of metabolites were defined during incubation with human liver microsomes, and subsequently, the metabolization was verified in in vivo study. In vitro metabolic profiling revealed the formation of nine major metabolites in the case of PC‐37 and eight metabolites of PC‐48. Hydroxylation and the enzymatic hydrolysis of bonds close to the piperazine ring appeared to be the principal metabolic pathways in vitro. Of these metabolites, M1–M7 of PC‐37 and M1–M6 of PC‐48 were confirmed under in vivo conditions. Pilot pharmacokinetic experiments in rats were focused on the absorption, distribution and elimination of these compounds. Absorption after i.m. application was relatively fast; the bioavailability expressed as AUCtotal was 28179 ± 4691 min.ng/mL for PC‐37 and 23374 ± 4045 min.ng/mL for PC‐48. Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma. The maximal brain concentrations are approximately two times higher than the plasma concentrations. The relatively high brain concentrations persisted throughout the experiment until 24 hr after application. Elimination via the kidneys (urine) significantly exceeded elimination via the liver (bile). All these characteristics are crucial for new candidates intended for AD treatment. The principle metabolic pathways that were verified in the in vivo study do not show any evidence for formation of extremely toxic metabolites, but this needs to be confirmed by further studies. 相似文献
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Aminopeptidase activity in strains of oral streptococci 总被引:2,自引:0,他引:2
Eugenie Floderus Carita Andersson Lars Linder Marie-Louise Sund 《Oral microbiology and immunology》1987,2(3):117-120
Ten strains of oral streptococci were analyzed for aminopeptidase activity by isoelectric focusing and crossed immunoelectrophoresis together with enzyme staining procedures. Substrate specificities were determined using 15 aminoacyl-β-naphthylamides. All 10 strains tested showed enzyme activity with the arginine and leucine substrates. None of the strains exhibited activity with the glycine, cystine, or proline substrates. Some strains had multiple enzyme bands with some of the substrates. All strains had aminopeptidase bands located in the pi range 4.1–4.3, except Streptococcus mutans IB and Streptococcus milleri NCTC 10708. The isoelectric profiles of these strains, having enzyme bands in the range 4.45–4.9, differed markedly from the others. These were also the only strains where no arginine aminopeptidase cross-reactivity occurred with the Streptococcus mitis ATCC 903 antiserum. 相似文献
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Porcine fetal enamel matrix derivative enhances bone formation induced by demineralized freeze dried bone allograft in vivo 总被引:7,自引:0,他引:7
Boyan BD Weesner TC Lohmann CH Andreacchio D Carnes DL Dean DD Cochran DL Schwartz Z 《Journal of periodontology》2000,71(8):1278-1286
BACKGROUND: Embryonic enamel matrix proteins are involved in the formation of acellular cementum during development of the periodontal attachment apparatus, suggesting that these proteins might be used clinically to promote periodontal regeneration. At present, it is unknown if these proteins are osteoinductive, osteoconductive, or osteopromotive. To address this question, we examined the ability of a commercially prepared embryonic porcine enamel matrix derivative to induce new bone formation in nude mouse calf muscle, or to enhance the bone induction ability of a demineralized freeze-dried bone allograft (DFDBA). METHODS: Porcine fetal enamel matrix derivative (EMD) was implanted bilaterally in the calf muscle of 4 male Nu/Nu mice per treatment group (N = 8 implants): 2 mg EMD alone; 4 mg EMD alone; inactive human DFDBA alone; inactive DFDBA + 2 mg EMD; inactive DFDBA + 4 mg EMD; active DFDBA alone; active DFDBA + 2 mg EMD; and active DFDBA + 4 mg EMD. Implants were harvested after 56 days and examined histologically for bone induction using a semi-quantitative score and histomorphometrically for area of new bone, cortical bone, bone marrow, and residual DFDBA. RESULTS: Implants containing inactive DFDBA, 2 mg EMD, 4 mg EMD, and inactive DFDBA + 2 or 4 mg EMD did not induce new bone. Active DFDBA and active DFDBA + 2 mg EMD induced new bone to a similar extent. In contrast, active DFDBA + 4 mg EMD resulted in enhanced bone induction, area of new bone, and cortical bone. Residual DFDBA was also increased in this group. CONCLUSIONS: EMD is not osteoinductive. However, it is osteopromotive, due in part to its osteoconductive properties, but a threshold concentration is required. 相似文献
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Mark Bangwei Tan Kim Ping Tan Joey Chan Yiing Beh Eugenie Yi Kar Chan Kenneth Fu Wen Chin Zong Yi Chin Wei Ming Chua Aaron Wei-Loong Chong Gary Tianyu Gu Wenlu Hou Anna Chooi Yan Lai Rebekah Zhuyi Lee Perry Jia Ren Liew May Yi Shan Lim Joshua Li Liang Lim Zehao Tan Eelin Tan Grace Siew Lim Tan Timothy Shao Ern Tan Eu Jin Tan Alexander Sheng Ming Tan Yet Yen Yan Winston Eng Hoe Lim 《Singapore medical journal》2021,62(1):8
The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore’s development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives. 相似文献
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