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71.
72.
A. Hess W. Bloch J. Rocker K. Addicks E. Stennert Olaf Michel 《European archives of oto-rhino-laryngology》1998,255(9):448-453
In order to demonstrate the involvement of nitric oxide synthases (NOS) – in particular the inducible isoform (iNOS) – in
inflammatory processes within the nasal airways, we used organ-bath incubation to study isolated inferior turbinates and mucosa
of the maxillary sinus of guinea pigs. The pattern of the expression in various substructures of the nasal mucosa was of special
interest. Mucosa was incubated for 6 h with lipopolysaccharides (LPS) produced by E. coli, interleukin II (IL-2) or tumor
necrosis factor-alpha (TNF-α). Saline was used as the control solution. Following incubation the specimens were fixed in buffered
4% formaldehyde solution over a period of 4 h. Tissues were next exposed to nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase-reaction
and immunostained with specific antibodies to iNOS. Results then showed a clearly increased or initiated expression of iNOS
in epithelium, glands, leucocytes and blood vessels of treated tissues in comparison to the control specimens. The inflammatory
mediator LPS and the cytokines Il-2 or TNF-α alone were found to be capable of increasing the expression of iNOS, although
the effects of LPS clearly exceeded those of the cytokines. This finding implicates iNOS-generated nitric oxide as a key factor
for causing nasal swelling, secretion and obstruction during nasal infections and allergic episodes.
Received: 18 November 1997 / Accepted: 22 April 1998 相似文献
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Gerhard Dongowski Bertram Fritzsch Jochen Giessler Albert H?rtl Olaf Kuhlmann Reinhard H H Neubert 《European journal of pharmaceutics and biopharmaceutics》2005,60(1):147-151
The bioavailability of orally administered drugs can be influenced by interactions with food components and by physico-chemical conditions in the upper gastrointestinal tract. Normally, bile salts enhance the transport of lipophilic drugs across mucosal membranes. Bile salts are able to form stable mixed micelles consisting of fatty acids and phospholipids. Conventional micellar systems are known to solubilize lipophilic drugs having a low bioavailability. The influence of bile salts and mixed micelles on the pharmacokinetics of the lipophilic drug quinine was investigated in rabbits. Female rabbits were given intraduadenally quinine (5 mg/kg body weight) without and with incorporation into the micellar or mixed micellar systems. Blood was collected every 30 min for 6 h. In plasma, concentration of quinine was measured using HPLC. The plasma concentration-time profiles of quinine were significantly lower within the first 2 h after administration in presence of both the sodium salt of glycodeoxycholic acid (above the critical micellar concentration) as well as of mixed micellar systems consisting of glycodeoxycholic acid and palmitic acid and/or lecithin. The pharmacokinetic parameters AUC (relative bioavailability) and c(max) of quinine were significantly decreased by micellar systems in rabbits. These mixed micellar systems lower and not as expected, increase the absorption of quinine in vivo. Therefore, quinine should be orally administered at least 1h before food intake, particularly before fat intake. 相似文献
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Monatsschrift Kinderheilkunde - 相似文献
78.
Chen Guang Yang Joseph Ciccolini Aurore Blesius Laetitia Dahan Danielle Bagarry-Liegey Caroline Brunet Arthur Varoquaux Nicolas Frances Hafedh Marouani Antoine Giovanni Rose-Marie Ferri-Dessens Mohamed Chefrour Roger Favre Florence Duffaud Jean-Fran?ois Seitz Michel Zanaret Bruno Lacarelle C��dric Mercier 《Cancer chemotherapy and pharmacology》2011,67(1):49-56
Background
Fluoropyrimidine drugs are widely used in head and neck cancer (HNC). DPD deficiency is a pharmacogenetics syndrome associated with severe/lethal toxicities upon 5-FU or capecitabine intake. We have developed a simple, rapid, and inexpensive functional testing for DPD activity, as a means to identify deficient patients and to anticipate subsequent 5-FU-related toxicities. We present here the impact of fluoropyrimidine dose tailoring based on DPD functional screening in a prospective, open, non-controlled study, both in term of reduction in severe toxicities and of treatment efficacy.Methods
About 65 patients with HNC (59?±?9?years, 52M/13F, Prospective Group) were entered into the study. Screening for DPD deficiency was performed prior to the beginning of the chemotherapy or radiochemotherapy. DPD status was evaluated by monitoring U/UH2 ratio levels in plasma as a surrogate marker for enzymatic functionality. 5-FU doses were reduced according to the extent of the detected DPD impairment, and adjusted on the basis of age, general condition, and other clinical/paraclinical covariates, if required. Treatment-related toxicities and subsequent impact on treatment delay were carefully monitored next for comparison with a retrospective, Reference subset of 74 other patients with HNC (mean age: 59?±?10, 58M/16F, Reference Group), previously treated in the same institute with similar schedule but using standard 5-FU dosage.Results
Thirty-one out of 65 patients (48%) were identified as mildly (28%) to markedly (20%) DPD deficient. Subsequently, dose reductions ranging from 10 to 100% with 5-FU were applied in those patients. In this group, six patients (9%) experienced severe toxicities, none of them being life threatening, and no toxic death was encountered. In comparison, 16 out of 74 patients (22%) of the Reference Group displayed severe side effects after standard 5-FU administration, 13% being life-threatening toxicities (e.g., G4 neutropenia?+?sepsis). Moreover, one toxic death was observed in this Reference Group. No postponement or cancelation of forthcoming chemoradiotherapy courses occurred in the Prospective Group, whereas treatment had to be disrupted in six patients (8%) from the Reference Group. No difference in first-line therapy efficacy was evidenced between the two subsets (78 vs. 79% response, P?=?0.790).Conclusions
Although non-randomized, this study strongly suggests that prospective determination of DPD status has an immediate clinical benefit by reducing the drug-induced toxicities incidence in patients treated with 5-FU, allowing an optimal administration of several courses in a row, while maintaining efficacy. Our preliminary results thus advocate for systematic DPD screening in patients eligible for treatment with fluoropyrimidine drugs in HNC. 相似文献79.
80.
Ruichong Ma Margarida Rei Isaac Woodhouse Katherine Ferris Sophie Kirschner Anandhakumar Chandran Uzi Gileadi Ji-Li Chen Mariana Pereira Pinho Yoanna Ariosa-Morejon Skirmantas Kriaucionis Nicola Ternette Hashem Koohy Olaf Ansorge Graham Ogg Puneet Plaha Vincenzo Cerundolo 《Neuro-oncology》2022,24(12):2093