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991.
Parathyroid hormone (PTH) secreted from parathyroid cells is a key regulator of circulating levels of calcium ion, which is maintained within a narrow physiological range mainly by the action of a cell surface Ca2+-sensing receptor (CaSR) residing on parathyroid cells. The CaSR belongs to the family C of G-protein-coupled receptors (GPCRs), all members of which have a large extra cellular domain called Venus flytrap, akin to bacterial nutrient sensor. Promiscuity of the CaSR is reflected in its binding to several physiologically relevant di- or polyvalent cations that could elicit cellular signaling, yet the ligand specificity remains poor. This problem has been circumvented by the discovery of calcimimetics, the positive allosteric modulators of the CaSR that activate the CaSR on parathyroid cells, immediately suppressing PTH secretion. Out of several small molecules that act as calcimimetics, cinacalcet is the most extensively studied. The discovery of the CaSR and these specific agonists provides important insights into the discovery of new drugs that will be discussed in this review from the perspective of their structure-activity relationship. The calcimimetic compound cinacalcet has obtained regulatory approval for the treatment of hyperparathyroidism and is the first positive allosteric modulator of any GPCR to reach the market. It has other important uses in dialysis patients with end-stage renal disease, in whom it decreases Ca X P product. Pharmaceutically converse to calcimimetics are calcilytic compounds, which antagonize parathyroid CaSR and stimulate PTH secretion. Antagonism of the CaSR has the potential to yield an anabolic therapy for osteoporosis that awaits clinical validation. 相似文献
992.
D. U. Bawankule S. K. Chattopadhyay A. Pal K. Saxena S. Yadav U. Faridi M. P. Darokar A. K. Gupta S. P. S. Khanuja 《Inflammopharmacology》2008,16(6):272-277
The effect of coumarinolignoid cleomiscosins A, B and C isolated from the plant Cleome viscosa on inflammatory mediators were studied in female swiss albino mice. A mixture of coumarinolignoid A, B, and C at 10, 30 and
100 mg/kg body weight once a day for 14 consecutive days were administered orally to the mice. Pro–inflammatory mediators
such as IL–6, TNF–α and nitric oxide were estimated from culture supernatant obtained from peritoneal macrophages stimulated
by LPS and anti-inflammatory mediator IL–4 was estimated from culture supernatant obtained from spleenocytes stimulated by
Con-A. For further confirmation, expressions of inflammatory mediators from serum and mortality rate were studied in LPS–induced
toxicity model in mice. The expression of Pro–inflammatory mediators was significantly (P <0.05) decreased in coumarinolignoids
treatment group in dose dependent manner, whereas the anti–inflammatory mediator expression was significantly increased in
coumarinolignoids at 10 mg/kg treatment. Mortality rate was also significantly reduced in treatment group in LPS–induced toxicity
model. The result of this study concluded that the oral administration of coumarinolignoids inhibited the pro–inflammatory
mediators and enhances the production of anti–inflammatory mediator in dose dependent manner.
Received 4 March 2008; accepted 17 July 2008 相似文献
993.
994.
Niladri Chattopadhyay Zhongli Cai Yongkyu Luke Kwon Eli Lechtman Jean-Philippe Pignol Raymond M. Reilly 《Breast cancer research and treatment》2013,137(1):81-91
The purpose of this study was to evaluate the effect of molecularly targeted gold nanoparticles (AuNPs) on tumor radiosensitization both in vitro and in vivo. Human Epidermal Growth Factor Receptor-2 (HER-2)-targeted AuNPs (Au–T) were synthesized by conjugating trastuzumab (Herceptin) to 30 nm AuNPs. In vitro, the cytotoxicity of Au-T or non-targeted AuNPs (Au–P) was assessed by γ-H2AX immunofluorescence microscopy for DNA damage and clonogenic survival assays. In vivo, athymic mice bearing subcutaneous MDA-MB-361 xenografts were treated with a single dose of 11 Gy of 100 kVp X-rays 24 h after intratumoral injection of Au–T (~0.8 mg of Au) or no X-radiation. Normal tissue toxicity was determined by hematology or biochemistry parameters. The combination of Au–P or Au–T with X-ray exposure increased the formation of γ-H2AX foci by 1.7 (P = 0.054) and 3.3 (P = 0.024) fold in comparison to X-radiation alone, respectively. The clonogenic survival of cells exposed to Au–T and X-rays was significantly lower from that of cells exposed to X-radiation alone, which translated to a dose enhancement factor of 1.6. In contrast, survival of cells exposed to Au–P and X-rays versus X-radiation alone were not significantly different. In vivo, the combination of Au–T and X-radiation resulted in regression of MDA-MB-361 tumors by 46 % as compared to treatment with X-radiation (16.0 % increase in tumor volume). No significant normal tissue toxicity was observed. Radiosensitization of breast cancer to X-radiation with AuNPs was successfully achieved with an optimized therapeutic strategy of molecular targeting of HER-2 and intratumoral administration. 相似文献
995.
Narendra M. Biswas Ranojoy Sen Gupta Alok Chattopadhyay Gargi Roy Choudhury Mohitosh Sarkar 《Reproductive toxicology (Elmsford, N.Y.)》2001,15(6):330-704
Cadmium-induced stress adversely affects testicular activity and causes sympathetic stimulation. To investigate the effect of atenolol, a β-adrenergic receptor blocker, on testicular androgen synthesis after cadmium treatment, adult Sprague-Dawley strain male rats were given a single sc dose of cadmium chloride 0.45 mg/kg BW. Animals were killed on day 3 after treatment. Adrenal weight, adrenal Δ5-3β-hydroxysteroid dehydrogenase (Δ5-3β-HSD) activity, serum corticosterone, and brain noradrenaline were increased significantly while testicular Δ5-3β-HSD and 17β-HSD activities, serum testosterone, and accessory sex organs weight were decreased. Oral coadministration of atenolol at a dose of 2.0 mg/kg body weight for 3 days resulted in complete protection of adrenal Δ5-3β-HSD, testicular Δ5-3β-HSD, and 17β-HSD activities, adrenal weight, serum corticosterone, and serum testosterone when compared with cadmium-only group and there were no significant differences in these parameters from the vehicle control values. Simultaneous administration of cadmium and atenolol also protected brain noradrenaline content and reduced the rise of testicular cadmium concentration. All the parameters were similar to control levels in rats treated with atenolol alone. We conclude that atenolol may protect testicular androgen synthesis by inhibiting the action of noradrenaline on testicular Leydig cells and adrenocortical hyperactivity in cadmium-treated rats. 相似文献
996.
997.
Alyssa Clay-Gilmour Subhayan Chattopadhyay Michelle A. T. Hildebrandt Hauke Thomsen Niels Weinhold Pavel Vodicka Ludmila Vodickova Per Hoffmann Markus M. Nthen Karl-Heinz Jckel Brge Schmidt Christian Langer Roman Hajek Gran Hallmans Ulrika Pettersson-Kymmer Claes Ohlsson Florentin Spth Richard Houlston Hartmut Goldschmidt Elisabet E. Manasanch Aaron Norman Shaji Kumar S. Vincent Rajkumar Susan Slager Asta Frsti Celine M. Vachon Kari Hemminki 《Blood cancer journal》2022,12(4)
998.
999.
Tanmoy Basak Carlos J. Gmez-García Rosa M. Gomila Antonio Frontera Shouvik Chattopadhyay 《RSC advances》2021,11(6):3315
The crystal structure and magnetic properties of two mononuclear iron(iii) Schiff base complexes, [FeL1(NCS)2] (1), HL1 = 2-[1-[[2-[(2-aminoethyl)amino]ethyl]imino]ethyl]phenol and [FeL2(N3)Cl] (2), HL2 = 2-(-1-(2-(2-aminoethylamino)ethylimino)ethyl)-4-methylphenol are reported. Each complex contains a Fe(iii) ion surrounded by a N3O Schiff base ligand and two NCS− ligands (in 1) or one N3− and one Cl− ligands (in 2). The magnetic properties can be well reproduced with zero field splittings in the high spin S = 5/2 Fe(iii) ions and weak intermolecular Fe–Fe interactions mediated by hydrogen bonds. This intermolecular antiferromagnetic interaction has been validated by using DFT calculations in complex 2. Moreover, the interaction energies of the H-bonded dimers in both complexes have been estimated using DFT calculations and characterized using a combination of QTAIM and NCI plot computational tools. Complexes 1 and 2 constitute two rare examples of Fe(iii) complexes with magnetic interactions through H-bonds.H-Bond mediated magnetic interactions in mononuclear iron(iii) Schiff base complexes were studied experimentally and validated by using DFT calculations. 相似文献
1000.
Ashalatha Ganesh Sourendra Kant Goswami Ratna Chattopadhyay Koel Chaudhury Baidyanath Chakravarty 《Journal of assisted reproduction and genetics》2009,26(1):19-24
Purpose Letrozole, though reported to be an effective ovulation inducing agent, warrants larger randomized trials. The purpose of
this study is to compare the efficacy of letrozole with that of rFSH and clomiphene citrate(CC)/rFSH for ovarian stimulation
in IUI cycles.
Methods Randomized, prospective, single-blinded clinical trial. 1387 PCOS women after CC failure were randomized into three groups:
Group A received letrozole, Group B received CC with two doses rFSH and Group C received continuous rFSH day 2 onwards until
hCG injection.
Results Group A, B and C had an ovulation rate of 79.30%, 56.95% and 89.89% and cycle cancellation rate of 20.70%, 43.05% and 10.11%,
respectively. Pregnancy rates in Group A, B and C were 23.39%, 14.35% and 17.92%, while the miscarriage rates were 13.80%,
16.67% and 14.52%, respectively.
Conclusion Letrozole appears to be a suitable ovulation inducing agent in PCOS women with CC failure and is found to be most effective
when baseline estradiol level >60 pg/ml.
Capsule Letrozole appears to be an effective ovulation inducing agent as compared to clomiphene-rFSH and continuous rFSH protocols
in PCOS women after clomiphene citrate failure. 相似文献