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41.
42.
Nigella sativa Supplementation Improves Asthma Control and Biomarkers: A Randomized,Double‐Blind,Placebo‐Controlled Trial 下载免费PDF全文
Abdulrahman Koshak Li Wei Emad Koshak Siraj Wali Omer Alamoudi Abdulrahman Demerdash Majdy Qutub Peter Natesan Pushparaj Michael Heinrich 《Phytotherapy research : PTR》2017,31(3):403-409
Poor compliance with conventional asthma medications remains a major problem in achieving asthma control. Nigella sativa oil (NSO) is used traditionally for many inflammatory conditions such as asthma. We aimed to investigate the benefits of NSO supplementation on clinical and inflammatory parameters of asthma. NSO capsules 500 mg twice daily for 4 weeks were used as a supplementary treatment in a randomized, double‐blind, placebo‐controlled trial in asthmatics (clinicaltrials.gov: NCT02407262). The primary outcome was Asthma Control Test score. The secondary outcomes were pulmonary function test, blood eosinophils and total serum Immunoglobulin E. Between 1 June and 30 December 2015, 80 asthmatics were enrolled, with 40 patients in each treatment and placebo groups. After 4 weeks, ten patients had withdrawn from each group. Compared with placebo, NSO group showed a significant improvement in mean Asthma Control Test score 21.1 (standard deviation = 2.6) versus 19.6 (standard deviation = 3.7) (p = 0.044) and a significant reduction in blood eosinophils by ?50 (?155 to ?1) versus 15 (?60 to 87) cells/μL (p = 0.013). NSO improved forced expiratory volume in 1 second as percentage of predicted value by 4 (?1.25 to 8.75) versus 1 (?2 to 5) but non‐significant (p = 0.170). This randomized, double‐blind, placebo‐controlled trial demonstrated that NSO supplementation improves asthma control with a trend in pulmonary function improvement. This was associated with a remarkable normalization of blood eosinophlia. Future studies should follow asthmatics for longer periods in a multicentre trial. Copyright © 2017 John Wiley & Sons, Ltd. 相似文献
43.
Murugesan N Tellew JE Gu Z Kunst BL Fadnis L Cornelius LA Baska RA Yang Y Beyer SM Monshizadegan H Dickinson KE Panchal B Valentine MT Chong S Morrison RA Carlson KE Powell JR Moreland S Barrish JC Kowala MC Macor JE 《Journal of medicinal chemistry》2002,45(18):3829-3835
The ET(A) receptor antagonist (2) (N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)-[1,1'-biphenyl]-2-sulfonamide, BMS-193884) shares the same biphenyl core as a large number of AT(1) receptor antagonists, including irbesartan (3). Thus, it was hypothesized that merging the structural elements of 2 with those of the biphenyl AT(1) antagonists (e.g., irbesartan) would yield a compound with dual activity for both receptors. This strategy led to the design, synthesis, and discovery of (15) (4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-[1,1'-biphenyl]-2-sulfonamide, BMS-248360) as a potent and orally active dual antagonist of both AT(1) and ET(A) receptors. Compound 15 represents a new approach to treating hypertension. 相似文献
44.
Regunathan A Cerny EA Villarreal J Bhattacharyya MH 《Toxicology and applied pharmacology》2002,185(1):25-40
Cadmium decreases bone mineral in mice and stimulates osteoclast formation and activity in cell culture. Bones from fos-deficient mice contain very few osteoclasts; src-/- bones contain osteoclasts that fail to activate. Fos-/- and src-/- mice develop osteopetrotic bones and their teeth do not erupt. These mice were used to determine if cadmium requires c-Fos or c-Src and secondarily functional osteoclasts to decrease bone mineral content. Mice heterozygous for fos deficiency were mated to produce fos-/- and fos+/o (wild-type) offspring. Pups were divided into four groups: fos+/o, Cd-; fos+/o, Cd+; fos-/-, Cd-; and fos-/-, Cd+. Cd+ pups received daily sc injections (50 microg Cd/kg) on days 17-20 and Cd in drinking water thereafter (10 ppm, days 21-27; 20 ppm, days 27-50). An analogous protocol was followed mating mice heterozygous for src deficiency. For acute exposures, 50-day-old mice were placed on a low-calcium diet and given two sequential 100 microg Cd doses by gavage, and feces were monitored for excretion of bone calcium. Continuous exposure results demonstrate that cadmium (1) significantly decreased bone calcium content (14-15%) and concentration (12-13%) in both fos+/o and fos-/- mice, (2) doubled multinucleated osteoclast-like cell number in fos-/- bones, and (3) stimulated tooth eruption in 40% of fos-/- mice. Cd gavage stimulated bone calcium excretion in both fos+/o and fos-/- mice. In contrast, cadmium had no effect on bones or teeth in src-/- mice. Results indicate that cadmium can decrease bone mineral via a c-Fos-independent pathway; however, c-Src is required for cadmium to stimulate bone remodeling and tooth eruption pathways. 相似文献
45.
Sridhar Natesan Greg E Reckless José N Nobrega Paul J Fletcher Shitij Kapur 《Neuropsychopharmacology》2006,31(9):1854-1863
The novel antipsychotic aripiprazole requires high (>90%) striatal D2 receptor occupancy (D2RO) to be clinically active, but despite its high D2RO it does not show extrapyramidal symptoms. While most antipsychotics are active at nearly 65% D2RO, they show motor side effects when D2RO exceeds 80%. We investigated this discrepancy between D2RO, 5HT2 receptor occupancy (5-HT2RO) and in vivo functional activity of aripiprazole in comparison to haloperidol (typical) and risperidone (atypical) in animal models. All three drugs showed dose-dependent D2RO. While risperidone clearly showed higher 5-HT2RO than D2RO, aripiprazole and haloperidol showed higher D2RO than 5-HT2RO at all doses. Haloperidol and risperidone induced catalepsy at doses producing >80% D2RO, while aripiprazole despite higher D2RO (>90%) induced no catalepsy. Haloperidol and risperidone's ED50 values for inhibition of conditioned avoidance response (CAR) and amphetamine-induced locomotor activity (AIL) corresponded to approximately 60% D2RO. In contrast, aripiprazole showed a significant dissociation; while it blocked AIL at similar D2RO, a 23-fold higher dose (86% D2RO) was required to inhibit CAR. FOS expression in shell region of the nucleus accumbens was significant for all drugs at D2ROs that were effective in CAR. However, in the core region of the nucleus accumbens and dorsolateral striatum, aripiprazole differed from the others in that despite high D2RO it induced low FOS. Haloperidol and risperidone showed dose/occupancy-dependent prolactin elevations, while aripiprazole did not. Across models, haloperidol and risperidone show similar occupancy-functional antagonism of the D2 system, while aripiprazole shows a clear dissociation. Partial agonism of aripiprazole offers a good explanation for this dissociation and provides a framework for understanding occupancy-functional relationships of partial D2 agonist antipsychotics. 相似文献
46.
Hongjian Zhang Donglu Zhang Wenying Li Ming Yao Celia D'Arienzo Yi-Xin Li William R Ewing Zhengxiang Gu Yeheng Zhu Natesan Murugesan Wen-Chyi Shyu W Griffith Humphreys 《Drug metabolism and disposition》2007,35(5):795-805
2-{Butyryl-[2'-(4,5-dimethyl-isoxazol-3-ylsulfamoyl)-biphenyl-4-ylmethyl]-amino}-N-isopropyl-3-methyl-butyramide (BMS-1) is a potent dual acting angiotensin-1 and endothelin-A receptor antagonist. The compound was subject to rapid metabolic clearance in monkey and human liver microsomes and exhibited low systemic exposure and marked interanimal variability in cynomolgus monkeys after p.o. administration. The variability pattern was identical to that of midazolam given p.o. in the same monkeys, as measured by area under the curve and Cmax values, suggesting that CYP3A-mediated metabolism might play a role in the rapid clearance and observed interanimal variability. Subsequent in vitro metabolism studies using human liver microsomes and cDNA-expressed human cytochrome P450 (P450) enzymes revealed that BMS-1 was a CYP3A4 substrate and was not metabolized by other human P450 enzymes. Mass spectral and NMR analyses of key metabolites led to the identification of the dimethyl isoxazole group as a major metabolic soft spot for BMS-1. Replacement of the 4-methyl group on the isoxazole ring with halogens not only improved overall metabolic stability but also decreased CYP3A-mediated hydroxylation of the isoxazole 5-methyl group. As exemplified by 2-{butyryl-[2'-(4-fluoro-5-methyl-isoxazol-3-ylsulfamoyl)-biphenyl-4-ylmethyl]-amino}-N-isopropyl-3-methyl-butyramide (BMS-3), a fluorinated analog of BMS-1, the structural modification resulted in an increase in the systemic exposure relative to previous analogs and a dramatic reduction in interanimal variability in the monkeys after p.o. administration. In addition, BMS-3 could be metabolized by both CYP2C9 and CYP3A4, thus avoiding the reliance on a single P450 enzyme for metabolic clearance. Integration of results obtained from in vitro metabolism studies and in vivo pharmacokinetic evaluations enabled the modulation of site-specific CYP3A-mediated metabolism, yielding analogs with improved overall metabolic profiles. 相似文献
47.
Attitudes and Beliefs Toward Supportive and Palliative Care Referral Among Hematologic and Solid Tumor Oncology Specialists 下载免费PDF全文
David Hui Minjeong Park Diane Liu Akhila Reddy Shalini Dalal Eduardo Bruera 《The oncologist》2015,20(11):1326-1332
Background.
Palliative care (PC) referrals are often delayed for patients with hematologic malignancies. We examined the differences in attitudes and beliefs toward PC referral between hematologic and solid tumor specialists and how their perception changed with use of the service name “supportive care” (SC).Materials and Methods.
We randomly surveyed 120 hematologic and 120 solid tumor oncology specialists at our tertiary care cancer center to examine their attitudes and beliefs toward PC and SC referral.Results.
Of the 240 specialists, 182 (76%) responded. Compared with solid tumor specialists, hematologic specialists were less likely to report that they would refer symptomatic patients with newly diagnosed cancer to PC (solid tumor, 43% vs. hematology, 21%; p = .002). A significantly greater proportion of specialists expressed that they would refer a patient with newly diagnosed cancer to SC than PC (solid tumor specialists: SC, 81% vs. PC, 43%; p < .001; hematology specialists: SC, 66% vs. PC, 21%; p < .001). The specialists perceived that PC was more likely than SC to be a barrier for referral (PC, 36% vs. SC, 3%; p < .001), to be synonymous with hospice (PC, 53% vs. SC, 6%; p < .001), to decrease hope (PC, 58% vs. SC, 8%; p < .001), and to be less appropriate for treatment of chemotherapy side effects (PC, 64% vs. SC, 19%; p < .001). On multivariate analysis, female clinicians (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.3-15.2; p = .02) and the perception that PC is a barrier for referral (OR, 3.0; 95% CI, 1.2-7.6; p = .02) were associated with PC referral if the service name “SC” was used.Conclusion.
Hematologic specialists were less likely to refer patients early in the disease trajectory and were conducive to referral with the service name SC instead of PC.Implications for Practice:
The present survey of oncology specialists found that hematologic specialists were less likely than solid tumor specialists to report that they would refer symptomatic patients with newly diagnosed cancer to palliative care. However, both groups were significantly more willing to refer patients early in the disease trajectory if the service name “supportive care” were used instead of “palliative care.” These findings suggest that rebranding might help to overcome the stigma associated with palliative care and improve patient access to palliative care services. 相似文献48.
Natesan Rajkumar Manickam Karthikeyan Dhanasekaran Soundarrajan Palanisami Dhanasekararaja Shanmuganathan Rajasekaran 《Indian Journal of Orthopaedics》2021,55(5):1111
PurposeThe aim of our study is to compare the efficacy of adductor canal block (ACB), periarticular local infiltration (PLI) and both combined (ACB + PLI) in multimodal pain management after TKA.MethodsThis is a prospective, randomized controlled double-blinded study undergoing primary unilateral TKA. They were randomized into three groups with fifty patients in each group: ACB alone (30 ml of 0.2% ropivacaine), PLI alone (30 ml 0.5% ropivacaine in 20 ml of normal saline), and both combined (ACB + PLI). The primary outcome studied was pain using visual analog score (VAS) in postoperative days (POD) 1 and 2. The secondary outcomes estimated were the ambulation capacity, the knee range of motion, need for rescue analgesia and length of hospital stay.ResultsThe mean VAS score was significantly lower at rest and after mobilization in the combined group (3.51 at POD 1, 2.04 at POD 2), compared with either alone group (ACB = 4.70, 2.86 versus PLI = 4.39, 3.41 at POD 1 and 2 respectively after mobilization, p < 0.001). The ambulation capacity (combined = 103.3 steps versus ACB = 98.1 and PLI = 95.2 steps, p = 0.04) and the knee range of motion (arc of motion 106.7 degrees versus ACB = 104.9 and PLI = 102.2 degrees, p = 0.004) were significantly higher in the combined group compared to the other groups. There was no significant difference in the length of stay between the groups (p = 0.12).ConclusionAdductor canal block combined with periarticular local infiltration provides better pain relief, good range of motion, quicker rehabilitation, and reduced opioid consumption. 相似文献
49.
Ramesh Venkatesh Sameeksha Agrawal Nikitha Gurram Reddy Akhila Sridharan Joshua Ong Naresh Kumar Yadav Jay Chhablani 《Indian journal of ophthalmology》2022,70(7):2506
Purpose:To study the retinal and choroidal thickness variations on enhanced depth imaging optical coherence tomography scans in ocular albinism (OA) and compare with age-matched healthy subjects.Methods: This retrospective observational study had 48 eyes of 24 patients diagnosed clinically as OA and age, sex, and axial length-matched control healthy subjects. All patients underwent detailed ophthalmic examination and a single-line horizontal-raster enhanced depth imaging – optical coherence tomography scan (Spectralis, Heidelberg Engineering). Retinal and choroidal thickness was measured, compared, and analyzed between the two groups. Mann–Whitney U test was used for analysis between the two groups. P < 0.05 was considered significant.Results: The mean age was 28.3 ± 11.6 and 29.9 ± 10.6 years in the OA group and control group, respectively. Spherical equivalents ranged from −8.5D to +10.5D in the OA group and from −8.0D to +10.0D in the control group. The mean axial length between the two groups (P = 0.652) were comparable. The average retinal thickness (272 ± 34.3 vs. 213 ± 13.8 mm; P < 0.001) was greater in the OA group as compared to controls. The mean choroidal thickness (184 ± 78.4 vs. 287 ± 46.4 mm; P < 0.001) was significantly thinner in the OA group.Conclusion: Acquisition of OCT scans in OA can be challenging. This study showed that the subfoveal retinal thickness and choroidal thickness measured across the scans were significantly different in the OA group compared to controls. In the future, more studies are required to evaluate the role of the choroid and its relationship to emmetropization in albinism. 相似文献
50.
Ali Haider MD Ahsan Azhar MD Kristy Nguyen PharmD Rony Dev DO Syed Mujtaba Ali Naqvi MD Syed Mussadiq Ali Naqvi MD Tonya Edwards APRN Akhila Reddy MD Shalini Dalal MD Kimberson C. Tanco MD Joseph Arthur MD Janet L. Williams MPH Minjeong Park PhD Diane D. Liu MS Seyedeh S. Dibaj PhD Eduardo Bruera MD 《Cancer》2019,125(24):4525-4531