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排序方式: 共有351条查询结果,搜索用时 15 毫秒
31.
Stephanie J. Tang Renuka Gupta Jennifer I. Lee Adrian M. Majid Parimal Patel Leigh Efird Angela Loo Shawn Mazur David P. Calfee Alexi Archambault Deanna Jannat-Khah Savira Kochhar Dargar Matthew S. Simon 《Joint Commission journal on quality and patient safety / Joint Commission Resources》2019,45(3):207-216
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Jayaraman Jayabharathi Annamalai Manimekalai Manoharan Padmavathy 《Medicinal chemistry research》2011,20(7):981-995
In a wide research program toward new and efficient antimicrobial agents, a series of substituted N-nitroso-3-alkyl piperidone oximes were synthesized and their antibacterial activity against Staphylococcus aureus, Pseudomonas aerugonisa, Escherichia coli, and Klbesiella pneumoniae and antifungal activity against Aspergillus niger, Aspergillus flavus, and Rhizopus were evaluated. Their structure and stereochemistry were characterized by high-resolution 1H NMR, mass and elemental analysis. The spectra of all N-nitroso oximes reveal the presence of two isomers labeled as E (–NOH group is anti to N–N=O moiety) and Z (–NOH group is syn to N–N=O moiety) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the
theoretical studies and coupling constant values, it was found that all N-nitroso oximes exist as an equilibrium mixture of CA boat conformation (B
1) and the major isomer was found to be E isomer. The molecular structure of N-nitroso oximes were also determined by semiempirical and Gaussian-03 calculation and the results are in agreement with the
experimental studies. 相似文献
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Biswarup Saha Ananda Mukherjee Saheli Samanta Piyali Saha Anup Kumar Ghosh Chitta Ranjan Santra Parimal Karmakar 《Toxicology in vitro》2009,23(6):1100-1109
Combined effects of alprazolam (Alp), a member of benzodiazepine group of drugs and caffeine on human cell lines, HeLa and THP1 were investigated in this study. Alp mediated cytotoxicity was enhanced while caffeine was present. The cell death was confirmed by observing morphological changes, LDH assay and membrane anisotropic study. Also such combined effects induced elevated level of ROS and depletion of GSH. The mechanism of cell death induced by simultaneous treatment of Alp and caffeine was associated with the calcium-mediated activation of μ-calpain, release of lysosomal protease cathepsin B, activation of PARP and cleavage of caspase 3. Our results indicate that, Alp alone induces apoptosis in human cells but in the presence of caffeine it augments necrosis in a well-regulated pathway. Thus our observations strongly suggest that, alprazolam and caffeine together produce severe cytotoxicity in human cell lines. 相似文献
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Cundy KC Annamalai T Bu L De Vera J Estrela J Luo W Shirsat P Torneros A Yao F Zou J Barrett RW Gallop MA 《The Journal of pharmacology and experimental therapeutics》2004,311(1):324-333
The absorption of gabapentin (Neurontin) is dose-dependent and variable between patients. Rapid clearance of the drug necessitates dosing three or more times per day to maintain therapeutic levels. These deficiencies appear to result from the low capacity, limited intestinal distribution, and variable expression of the solute transporter responsible for gabapentin absorption. Saturation of this transporter at doses used clinically leads to unpredictable drug exposure and potentially ineffective therapy in some patients. XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl]aminomethyl)-1-cyclohexane acetic acid] is a novel prodrug of gabapentin designed to be absorbed by high-capacity nutrient transporters located throughout the intestine. XP13512 was efficiently absorbed and rapidly converted to gabapentin after oral dosing in rats and monkeys. Exposure to gabapentin was proportional to prodrug dose, whereas exposure to intact XP13512 was low. In rats, >95% of an oral dose of (14)C-XP13512 was excreted in urine in 24 h as gabapentin. In monkeys, oral bioavailability of gabapentin from XP13512 capsules was 84.2% compared with 25.4% after a similar oral Neurontin dose. Compared with intracolonic gabapentin, intracolonic XP13512 gave a 17-fold higher gabapentin exposure in rats and 34-fold higher in monkeys. XP13512 may therefore be incorporated into a sustained release formulation to provide extended gabapentin exposure. XP13512 demonstrated improved gabapentin bioavailability, increased dose proportionality, and enhanced colonic absorption. In clinical use, XP13512 may improve the treatment of neuropathic pain, epilepsy, and numerous other conditions by increasing efficacy, reducing interpatient variability, and decreasing frequency of dosing. 相似文献
39.
Platelets are known to process human factor V during secretion and/or membrane binding. We studied the functional and structural changes produced in human factor V by purified human platelet calpain (calcium- activated thiol protease) and compared the alterations with those induced by thrombin. A maximum increase in coagulant activity of 2.5- fold was observed when factor V (1 U/mL, 33 nmol/L) was incubated with calpain (0.03 U/mL, 2.7 nmol/L) in comparison with a 8.8-fold increment for alpha-thrombin (0.7 U/mL, 8 nmol/L) at 25 degrees C. Thrombin additions to reactions initiated by calpain resulted in further activation comparable to that of thrombin alone, whereas the subsequent addition of calpain had no effect on the extent or pattern of the activation of factor V by thrombin. The cleavage pattern of factor V produced by these two enzymes are distinctly different. Although thrombin activation eventually results in four final components designated C1 (150 kd), D (105 kd), E (71 kd), and F1F2 (71 to 74 kd), calpain yields initial components of 200 kd and 160 kd within one minute. Further digestion of the 200 kd species by calpain gives rise first to a polypeptide of 160 kd that is converted to a 140 kd and a 120 kd species by two minutes with an increase in coagulant activity. Immunoblotting of these fragments with the monoclonal antibody (MoAb) B10 directed to factor V and the thrombin-generated C1 fragment yields results demonstrating a common epitope in these calpain-generated components of 200, 160, 140 and 120 kd. The degradation of the initial 160 kd polypeptide gives rise to polypeptides of 100 and 65 kd, both undetectable on immunoblotting with MoAb B10. The 130, 87, 58, and 48 kd components are of less certain origin. Thus, platelet calpain generates a complex but reproducible cleavage pattern different from thrombin that may explain the partial activation observed. Nevertheless, calpain processing may play a role in early hemostatic reactions involving platelets before the appearance of the first thrombin molecule. 相似文献