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891.
The processes by which the body handles drugs and which determine the temporal profile of drug concentrations in the body can be conveniently categorized into: absorption —process of drug transport from the site of release of drug from the delivery system into the systemic blood circulation; distribution —process of reversible transport of drug molecules from the site of absorption to those tissues of the body into which the drug is able to distribute; and elimination —process of irreversible removal of drug molecules from the body. Elimination of drug from the body will occur by metabolism—chemical modification of drug, and/or excretion—physical removal of drug from the body, e.g. renal or biliary excretion. This article first discusses the composition and structure of mammalian cell membranes, as this is fundamental to understanding the relationship between a drug's physicochemical properties and its membrane transport, and as a corollary, the understanding of the processes of drug absorption, distribution and elimination. Mechanisms involved in the absorption, distribution and elimination of pharmaceuticals are then discussed through integration of mammalian physiology, biochemistry and drug physicochemical properties. Further, the effect of changes in the above processes upon drug concentration-time profiles in the body is considered. 相似文献
892.
893.
Erkert RS MacAllister CG Payton ME Clarke CR 《American journal of veterinary research》2005,66(2):284-288
OBJECTIVE: To use force plate analysis to evaluate the analgesic efficacies of flunixin meglumine and phenylbutazone administered i.v. at typical clinical doses in horses with navicular syndrome. ANIMALS: 12 horses with navicular syndrome that were otherwise clinically normal. PROCEDURE: Horses received flunixin (1.1 mg/kg), phenylbutazone (4.4 mg/kg), or physiologic saline (0.9% NaCI; 1 mL/45 kg) solution administered IV once daily for 4 days with a 14-day washout period between treatments (3 treatments/horse). Before beginning treatment (baseline) and 6, 12, 24, and 30 hours after the fourth dose of each treatment, horses were evaluated by use of the American Association of Equine Practitioners lameness scoring system (half scores permitted) and peak vertical force of the forelimbs was measured via a force plate. RESULTS: At 6, 12, and 24 hours after the fourth treatment, subjective lameness evaluations and force plate data indicated significant improvement in lameness from baseline values in horses treated with flunixin or phenylbutazone, compared with control horses; at those time points, the assessed variables in flunixin- or phenylbutazone-treated horses were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with navicular syndrome treated once daily for 4 days, typical clinical doses of flunixin and phenylbutazone resulted in similar significant improvement in lameness at 6, 12, and 24 hours after the final dose, compared with findings in horses treated with saline solution. The effect of flunixin or phenylbutazone was maintained for at least 24 hours. Flunixin meglumine and phenylbutazone appear to have similar analgesic effects in horses with navicular syndrome. 相似文献
894.
Mattson SE Pearce SG Bouré LP Dobson H Hurtig MB Black WD 《American journal of veterinary research》2005,66(7):1267-1272
OBJECTIVE: To describe and compare the distribution of technetium Tc 99m (99mTc) pertechnate following intraosseous or i.v. injection (with or without use of a tourniquet) in the distal portion of the forelimb in standing horses. ANIMALS: 4 horses. PROCEDURE: Each horse received 4 forelimb treatments in random sequence: intraosseous infusion with tourniquet application (IOT), intraosseous infusion without tourniquet application, i.v infusion with tourniquet application (IVT), and i.v. infusion without tourniquet application. Dynamic nuclear scintigraphic imaging of the third metacarpal bone, proximal and middle phalanges, and distal phalanx was performed from the start of each treatment until 1 hour after infusion was completed. Radionuclide activity was compared within and between treatment groups. RESULTS: Tourniquet application was necessary to maintain high levels of radionuclide activity in the distal portion of the forelimb after intraosseous or i.v. infusion with 99mTc pertechnate; IVT and IOT treatments resulted in similar radionuclide activity in the proximal and middle phalanges and distal phalanx. Of the 4 treatments, there was significantly higher radionuclide activity in the distal aspect of the third metacarpal bone after the IOT treatment. CONCLUSIONS AND CLINICAL RELEVANCE: By use of a tourniquet, radionuclide administration via the intraosseous or i.v. routes resulted in effective perfusion of the distal portion of the forelimb and similar distribution of the agent in the phalanges of horses. Further studies are required to ascertain whether these findings apply to delivery of therapeutic agents in infected tissues via IOT or IVT. 相似文献
895.
Lawler DF Evans RH Larson BT Spitznagel EL Ellersieck MR Kealy RD 《Journal of the American Veterinary Medical Association》2005,226(2):225-231
OBJECTIVE: To describe effects of lifetime food restriction on causes of death and the association between body-mass characteristics and time of death in dogs. DESIGN: Paired-feeding study. ANIMALS: 48 dogs from 7 litters. PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less food than its pair mate from 8 weeks of age until death. Numerous morphometric and physiologic measures were obtained at various intervals throughout life. Associations of feeding group to time and causes of death were evaluated, along with important associated factors such as body composition components and insulin-glucose responses. RESULTS: Median life span was significantly longer for the group that was fed 25% less food, whereas causes of death were generally similar between the 2 feeding groups. High body-fat mass and declining lean mass significantly predicted death 1 year prior to death, and lean body composition was associated with metabolic responses that appeared to be integrally involved in health and longevity. CONCLUSIONS AND CLINICAL RELEVANCE: Results were similar to results of diet restriction studies in rodents and primates, reflecting delayed death from species- and strain-specific intrinsic causes. Clinicians should be aware that unplanned body mass changes during mid- and later life of dogs may indicate the need for thorough clinical evaluation. 相似文献
896.
Hill KE Scott-Moncrieff JC Koshko MA Glickman LT Glickman NW Nelson RW Blevins WE Oliver JW 《Journal of the American Veterinary Medical Association》2005,226(4):556-561
OBJECTIVE: To evaluate adrenal sex hormone concentrations in response to ACTH stimulation in healthy dogs, dogs with adrenal tumors, and dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN: Prospective study. ANIMALS: 11 healthy control dogs, 9 dogs with adrenal-dependent hyperadrenocorticism (adenocarcinoma [ACA] or other tumor); 11 dogs with PDH, and 6 dogs with noncortisol-secreting adrenal tumors (ATs). PROCEDURE: Hyperadrenocorticism was diagnosed on the basis of clinical signs; physical examination findings; and results of ACTH stimulation test, low-dose dexamethasone suppression test, or both. Dogs with noncortisol-secreting ATs did not have hyperadrenocorticism but had ultrasonographic evidence of an AT. Concentrations of cortisol, androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone were measured before and 1 hour after i.m. administration of 0.25 mg of synthetic ACTH. RESULTS: All dogs with ACA, 10 dogs with PDH, and 4 dogs with ATs had 1 or more sex hormone concentrations greater than the reference range after ACTH stimulation. The absolute difference for progesterone, 17-hydroxyprogesterone, and testosterone concentrations (value obtained after ACTH administration minus value obtained before ACTH administration) was significantly greater for dogs with ACA, compared with the other 3 groups. The absolute difference for androstenedione was significantly greater for dogs with ACA, compared with dogs with AT and healthy control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with ACA secrete increased concentrations of adrenal sex hormones, compared with dogs with PDH, noncortisol-secreting ATs, and healthy dogs. Dogs with noncortisol-secreting ATs also have increased concentrations of sex hormones. There is great interdog variability in sex hormone concentrations in dogs with ACA after stimulation with ACTH. 相似文献
897.
OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of morphine after IV administration as an infusion or multiple doses in dogs by use of a von Frey (vF) device. ANIMALS: 6 dogs. PROCEDURE: In the first 2 crossover experiments of a 3-way crossover study, morphine or saline (0.9%) solution was administered via IV infusion. Loading doses and infusion rates were administered to attain targeted plasma concentrations of 10, 20, 30, and 40 ng/mL. In the third experiment, morphine (0.5 mg/kg) was administered IV every 2 hours for 3 doses. The vF thresholds were measured hourly for 8 hours. Plasma concentrations of morphine were measured by high-pressure liquid chromatography. RESULTS: No significant changes in vF thresholds were observed during infusion of saline solution. The vF thresholds were significantly increased from 5 to 8 hours during the infusion phase, corresponding to targeted morphine plasma concentrations > 30 ng/mL and infusion rates > or = 0.15 +/- 0.02 mg/kg/h.The maximal effect (EMAX) was 78 +/- 11% (percentage change from baseline), and the effective concentration to attain a 50% maximal response (EC50) was 29.5 +/- 5.4 ng/mL. The vF thresholds were significantly increased from 1 to 7 hours during the multiple-dose phase; the EC50 and EMAX were 23.9 +/- 4.7 ng/mL and 173 +/- 58%, respectively. No significant differences in half-life, volume of distribution, or clearance between the first and last dose of morphine were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine administered via IV infusion (0.15 +/- 0.02 mg/kg/h) and multiple doses (0.5 mg/kg, IV, every 2 hours for 3 doses) maintained significant antinociception in dogs. 相似文献
898.
Haskins M Jezyk P Giger U 《Journal of the American Veterinary Medical Association》2005,226(7):1047; author reply 1047
899.
900.
Evaluation of transdermal application of glipizide in a pluronic lecithin gel to healthy cats 总被引:1,自引:0,他引:1
Bennett N Papich MG Hoenig M Fettman MJ Lappin MR 《American journal of veterinary research》2005,66(4):581-588
OBJECTIVE: To evaluate plasma glipizide concentration and its relationship to plasma glucose and serum insulin concentrations in healthy cats administered glipizide orally or transdermally. ANIMALS-15 healthy adult laboratory-raised cats. PROCEDURE: Cats were randomly assigned to 2 treatment groups (5 mg of glipizide, PO or transdermally) and a control group. Blood samples were collected 0, 10, 20, 30, 45, 60, 90, and 120 minutes and 4, 6, 10, 14, 18, and 24 hours after administration to determine concentrations of insulin, glucose, and glipizide. RESULTS: Glipizide was detected in all treated cats. Mean +/- SD transdermal absorption was 20 +/- 14% of oral absorption. Mean maximum glipizide concentration was reached 5.0 +/- 3.5 hours after oral and 16.0 +/- 4.5 hours after transdermal administration. Elimination half-life was variable (16.8 +/- 12 hours orally and 15.5 +/- 15.3 hours transdermally). Plasma glucose concentrations decreased in all treated cats, compared with concentrations in control cats. Plasma glucose concentrations were significantly lower 2 to 6 hours after oral administration, compared with after transdermal application; concentrations were similar between treatment groups and significantly lower than for control cats 10 to 24 hours after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Transdermal absorption of glipizide was low and inconsistent, but analysis of our results indicated that it did affect plasma glucose concentrations. Transdermal administration of glipizide is not equivalent to oral administration. Formulation, absorption, and stability studies are required before clinical analysis can be performed. Transdermal administration of glipizide cannot be recommended for clinical use at this time. 相似文献