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101.
Antibacterial,antioxidant and anti-proliferative properties and zinc content of five south Portugal herbs 总被引:1,自引:0,他引:1
Ricardo Nunes Pawel Pasko Malgorzata Tyszka-Czochara Agnieszka Szewczyk Marek Szlosarczyk 《Pharmaceutical biology》2017,55(1):114-123
Context: Crataegus monogyna L. (Rosaceae) (CM), Equisetum telmateia L. (Equisataceae) (ET), Geranium purpureum Vil. (Geraniaceae) (GP), Mentha suaveolens Ehrh. (Lamiaceae) (MS), and Lavandula stoechas L. spp. luisieri (Lamiaceae) (LS) are all medicinal.Objective: To evaluate the antioxidant, antiproliferative and antimicrobial activities of plant extracts and quantify individual phenolics and zinc.Material and methods: Aerial part extracts were prepared with water (W), ethanol (E) and an 80% mixture (80EW). Antioxidant activity was measured with TAA, FRAP and RP methods. Phenolics were quantified with a HPLC. Zinc was quantified using voltammetry. Antibacterial activity (after 48?h) was tested using Enterococcus faecalis, Bacillus cereus, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Listeria monocytogenes. Antiproliferative activity (after 24?h) was tested using HEP G2 cells and fibroblasts.Results: Solvents influenced results; the best were E and 80EW. GP had the highest antioxidant activity (TAA and FRAP of 536.90?mg AAE/g dw and 783.48?mg TE/g dw, respectively). CM had the highest zinc concentration (37.21?mg/kg) and phenolic variety, with neochlorogenic acid as the most abundant (92.91?mg/100?g dw). LS was rich in rosmarinic acid (301.71?mg/100?g dw). GP and LS inhibited the most microorganisms: B. cereus, E. coli and S. aureus. GP also inhibited E. faecalis. CM had the lowest MIC: 5830?μg/mL. The antibacterial activity is explained by the phenolics present. LS and CM showed the most significant anti-proliferative activity, which is explained by their zinc content.Conclusion: The most promising plants for further studies are CM, LS and GP. 相似文献
102.
Pawel Petkow Dimitrow Joanna Michaowska Danuta Sorysz 《Echocardiography (Mount Kisco, N.Y.)》2010,27(6):603-607
Background: The aim of the study was to assess the effect of hemodialysis (HD) on left ventricular outflow tract gradient (LVOTG) measured both in supine and upright position (provocative maneuver to unload LV cavity by rapid preload reduction). Supine/standing echocardiography was performed immediately before and immediately after HD. For additional verification of the hypothesis about preload‐dependence of LVOTG, the echocardiograms after long (2‐day delay HD due to weekend) versus short (usual 1‐day) pause between HDs were compared. Methods: Forty‐one patients on chronic HD (mean age 44 ± 11 years) were examined using a portable hand‐carried echocardiograph. In accordance with the prestudy assumption the ultrafiltration volume was significantly greater during HD after a long pause in comparison to HD after a short pause (3707 ± 2826 mL vs. 2665 ± 1152 mL P < 0.05). Results: After a long pause, the mean value of LVOTG at the pre‐HD was mildly increased in the supine position and remained at a similar level in the upright position (13.1 ± 6.1 vs. 13.6 ± 9.1 mmHg). Mean LVOTG at the post‐HD in the supine position was similar to pre‐HD, however the orthostatic stress test induced a significant increase of LVOTG (13.9 ± 15.2 vs. 18.2 ± 19.9 mmHg P < 0.05). After a short pause at the pre‐HD the LVOTG in the supine position and after the orthostatic provocation was very similar to measurements after long pause (13.3 ± 9.1 vs. 13.3 ± 10.8 mmHg). At the post‐HD the mean value of LVOTG increased during upright posture but the differences were of borderline significance (13.2 ± 6.6 vs. 17.9 ± 18.6 mmHg P = 0.052). Conclusions: HD predisposed to standing‐provoked LVOTG especially when a long pause (2 days) between HDs induced a greater weight gain and subsequently a larger volume of ultrafiltration was needed to reduce hypervolemia. (Echocardiography 2010;27:603‐607) 相似文献
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Objective To examine the association of serum hormone levels with all‐cause mortality in older community‐dwelling men. Design Single centre cohort study. Subjects Men aged 50 and older, insured by Société de Secours Minière de Bourgogne (Montceau les Mines, France). Among 3400 men invited to participate, 782 volunteers had serum hormone measurements and were followed up for 10 years. No exclusion criteria were used. Results Nonsurvivors (n = 182) were older, had more comorbidities and lower physical performance. The lowest quartile of 25‐hydroxycholecalciferol (25OHD) level predicted mortality [HR = 1·44, 95% confidence interval (CI): 1·03–2·03, P < 0·05] regardless of age, BMI, smoking, physical activity, vitamin D supplementation, and health status; mainly for the first 3 years. The 17β‐E2 level predicted mortality independent of confounders after the third year (HR = 1·21 per 1 SD increase, 95% CI: 1·09–1·35, P < 0·001). In the fully adjusted models, risk of death increased per quartiles of 17β‐E2 (trend –P < 0·001) and was higher in the third and the fourth quartiles compared with the lowest quartile (HR = 1·80, 95% CI: 1·09–2·98, P < 0·05 and HR = 2·83, 95% CI: 1·71–4·67, P < 0·001). Concentrations of testosterone and PTH did not predict mortality independent of the model. Conclusions In older men, increased 17β‐E2 level predicted mortality after 3 years of follow‐up. Thus, high 17β‐E2 level may reflect presence of risk factors precipitating development of diseases. Low 25OHD level predicted mortality more weakly, mainly for the first 3 years of the follow‐up, and was strongly influenced by the confounding variables. Thus, low 25OHD level may reflect poor current health status and unhealthy lifestyle. 相似文献
105.
Julia V. Gerasimenko Oleksiy Gryshchenko Pawel E. Ferdek Eloise Stapleton Tania O. G. Hébert Solomiia Bychkova Shuang Peng Malcolm Begg Oleg V. Gerasimenko Ole H. Petersen 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(32):13186-13191
Alcohol-related acute pancreatitis can be mediated by a combination of alcohol and fatty acids (fatty acid ethyl esters) and is initiated by a sustained elevation of the Ca2+ concentration inside pancreatic acinar cells ([Ca2+]i), due to excessive release of Ca2+ stored inside the cells followed by Ca2+ entry from the interstitial fluid. The sustained [Ca2+]i elevation activates intracellular digestive proenzymes resulting in necrosis and inflammation. We tested the hypothesis that pharmacological blockade of store-operated or Ca2+ release-activated Ca2+ channels (CRAC) would prevent sustained elevation of [Ca2+]i and therefore protease activation and necrosis. In isolated mouse pancreatic acinar cells, CRAC channels were activated by blocking Ca2+ ATPase pumps in the endoplasmic reticulum with thapsigargin in the absence of external Ca2+. Ca2+ entry then occurred upon admission of Ca2+ to the extracellular solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A, inhibited store-operated Ca2+ entry in a concentration-dependent manner within the range of 1 to 50 μM (IC50 = 3.4 μM), but had little or no effect on the physiological Ca2+ spiking evoked by acetylcholine or cholecystokinin. Palmitoleic acid ethyl ester (100 μM), an important mediator of alcohol-related pancreatitis, evoked a sustained elevation of [Ca2+]i, which was markedly reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced trypsin and protease activity as well as necrosis were almost abolished by blocking CRAC channels. There is currently no specific treatment of pancreatitis, but our data show that pharmacological CRAC blockade is highly effective against toxic [Ca2+]i elevation, necrosis, and trypsin/protease activity and therefore has potential to effectively treat pancreatitis. 相似文献
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108.
Denis C Talbot Joachim von Pawel Emma Cattell S Murray Yule Claire Johnston Anthe S Zandvliet Alwin D R Huitema Chris J Norbury Paul Ellis Leon Bosquee Martin Reck 《Clinical cancer research》2007,13(6):1816-1822
PURPOSE: The primary aim of this study was to measure the objective tumor response rate following treatment with indisulam [E7070; N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide] as second-line therapy in patients with advanced non-small cell lung cancer. The secondary aims were to determine progression-free survival, to assess the safety and tolerability of indisulam, and to study its pharmacokinetic and pharmacodynamic profile. EXPERIMENTAL DESIGN: Patients were randomized to receive indisulam every 3 weeks either as a single i.v. dose of 700 mg/m(2) on day one (dx1) or 130 mg/m(2) given on days 1 to 5 inclusive as a daily infusion (dx5). All patients had previously received platinum-based chemotherapy. RESULTS: Forty-four patients were randomized. Only minor responses were seen. Myelosuppression, gastrointestinal symptoms, and lethargy were the most common toxicities and were more frequent in the dx1 arm. The pharmacokinetics of indisulam in each treatment schedule were adequately described using a previously developed population pharmacokinetic model and were mostly consistent with the results of the phase I program. Flow cytometric analysis of endobronchial and metastatic disease revealed a reduction in the fraction of cycling cells and an increase in apoptosis following indisulam compared with pretreatment levels. CONCLUSIONS: We conclude that, despite evidence of tumor-specific indisulam-induced apoptosis, neither of these treatment schedules has single-agent activity as second-line treatment of non-small cell lung cancer. 相似文献
109.
Martin MB Sanders JM Kendrick H de Luca-Fradley K Lewis JC Grimley JS Van Brussel EM Olsen JR Meints GA Burzynska A Kafarski P Croft SL Oldfield E 《Journal of medicinal chemistry》2002,45(14):2904-2914
We report the results of a comparative molecular field analysis (CoMFA) investigation of the growth inhibition of the bloodstream form of Trypanosoma brucei rhodesiense trypomastigotes by bisphosphonates. A quantitative three-dimensional structure-activity relationship CoMFA model for a set of 26 bisphosphonates having a range of activity spanning approximately 3 orders of magnitude (minimum IC(50) = 220 nM; maximum IC(50) = 102 microM) yielded an R(2) value of 0.87 with a cross-validated R(2) value of 0.79. The predictive utility of this approach was tested for three sets of three compounds: the average pIC(50) error was 0.23. For the nitrogen-containing bisphosphonates, in general, the activity was aromatic- > aliphatic-containing side chains. The activity of aromatic species lacking an alkyl ring substitution decreased from ortho to meta to para substitution; halogen substitutions also reduced activity. For the aliphatic bisphosphonates, the IC(50) values decreased nearly monotonically with increasing chain length (down to IC(50) = 2.0 microM for the n-C(11) alkyl side chain species). We also show, using a "rescue" experiment, that the molecular target of the nitrogen-containing bisphosphonate, risedronate, in T. b. rhodesiense is the enzyme farnesyl pyrophosphate synthase. In addition, we report the LD(50) values of bisphosphonates in a mammalian cell general toxicity screen and present a comparison between the therapeutic indices and the IC(50) values in the T. b. rhodesiense growth inhibition assay. Several bisphosphonates were found to have large therapeutic indices (> or =200:1) as well as low IC(50) values, suggesting their further investigation as antiparasitic agents against T. b. rhodesiense. 相似文献
110.
Zaniboni M Rossini A Swietach P Banger N Spitzer KW Vaughan-Jones RD 《Circulation research》2003,93(8):726-735
Although protons can directly or indirectly gate solute permeability of the myocardial gap junction, there is little information regarding their own permeation, despite their importance in the regulation of myocardial contractility and rhythm. By pipette-loading of acid into guinea pig isolated, ventricular myocyte pairs while imaging pH(i) confocally using SNARF fluorescence, we have observed that protons permeate the junctional region. Permeation is inhibited by glycyrrhetinic acid, an agent that also increases intercellular electrical resistance, suggesting H+ permeation via gap junctions. The rate of spread of acid between cells appears to be limited by junctional permeation rather than by cytoplasmic diffusion. Mathematical analyses, combined with experiments using SNARF as a proton carrier, suggest that gap junctional H+ transmission may be accomplished physiologically by the permeation of intrinsic "proton-porter" molecules. We propose that proton flux through gap junctions will contribute to the dissipation of regional acid loads within the myocardium. This represents a mechanism for the local control of myocardial pH(i). 相似文献