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91.
92.
CZ Zhu JP Mikusa Y Fan PR Hollingsworth M Pai P Chandran AV Daza BB Yao MJ Dart MD Meyer MW Decker GC Hsieh P Honore 《British journal of pharmacology》2009,157(4):645-655
Background and purpose:
Activation of cannabinoid (CB) receptors decreases nociceptive transmission in inflammatory or neuropathic pain states. However, the effects of CB receptor agonists in post-operative pain remain to be investigated. Here, we characterized the anti-allodynic effects of WIN 55,212-2 (WIN) in a rat model of post-operative pain.Experimental approach:
WIN 55,212-2 was characterized in radioligand binding and in vitro functional assays at rat and human CB1 and CB2 receptors. Analgesic activity and site(s) of action of WIN were assessed in the skin incision-induced post-operative pain model in rats; receptor specificity was investigated using selective CB1 and CB2 receptor antagonists.Key results:
WIN 55,212-2 exhibited non-selective affinity and agonist efficacy at human and rat CB1 versus CB2 receptors. Systemic administration of WIN decreased injury-induced mechanical allodynia and these effects were reversed by pretreatment with a CB1 receptor antagonist, but not with a CB2 receptor antagonist, given by systemic, intrathecal and supraspinal routes. In addition, peripheral administration of both CB1 and CB2 antagonists blocked systemic WIN-induced analgesic activity.Conclusions and implications:
Both CB1 and CB2 receptors were involved in the peripheral anti-allodynic effect of systemic WIN in a pre-clinical model of post-operative pain. In contrast, the centrally mediated anti-allodynic activity of systemic WIN is mostly due to the activation of CB1 but not CB2 receptors at both the spinal cord and brain levels. However, the increased potency of WIN following i.c.v. administration suggests that its main site of action is at CB1 receptors in the brain.British Journal of Pharmacology (2009) 157, 645–655; doi:10.1111/j.1476-5381.2009.00184.x; published online 3 April 2009 相似文献93.
Ho AD; Ganeshaguru K; Knauf WU; Dietz G; Trede I; Hunstein W; Hoffbrand AV 《Blood》1988,72(6):1884-1890
Deoxycoformycin (DCF), an adenosine deaminase (ADA) inhibitor, has been shown to be active in lymphoid neoplasms. The mechanism of cytotoxicity might involve accumulation of deoxyadenosine triphosphate (dATP), depletion of the nicotinamide adenine dinucleotide (NAD) and ATP pool, induction of double-stranded DNA strand breaks, or inhibition of S- adenosyl homocysteine hydrolase (SAH-hydrolase). We have investigated the biochemical changes in the circulating malignant cells of patients with chronic leukemia/lymphoma who were treated with DCF (4 mg/m2 weekly). Blood samples were taken from 17 patients with 60% or more circulating leukemic cells before, 4, 24, and 48 hours and five days after the first administration of DCF. Leukemic cells were separated and studied for changes in ADA, dATP, ATP, NAD, and SAH-hydrolase levels and DNA strand breaks and the data analyzed according to clinical response. Inhibition of ADA activity was found in all except one patient at 4 to 24 hours after the first administration of DCF. dATP started to accumulate at four hours, reached a maximum level between 24 and 48 hours, and returned to base values on the fifth day. Intracellular ATP and NAD levels were transiently reduced in some of the patients. However, no correlation between these changes and a clinical response could be found. DNA strand breaks could be studied in 13 patients. A significant increase in DNA breaks at 24 to 48 hours was found in six of the seven responders but only in one of the six nonresponders. At 24 hours, SAH-hydrolase levels were reduced in all seven responders studied, but only in two of the seven nonresponders. The difference in inhibition of SAH-hydrolase was statistically significant (P = .0023). These results suggest that DNA strand breaks and inhibition of SAH-hydrolase correlate with clinical response. 相似文献
94.
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96.
DG Schroeder B. Torún AV Bartlett H. Miracle-McMahill 《Acta paediatrica (Oslo, Norway : 1992)》1997,86(11):1155-1161
A community-based, randomized trial was conducted to evaluate a locally available diet for the management of acute diarrhea ( n = 99 episodes) in 90 Guatemalan children, 4–42 months of age. The Test Diet (TD), a combination of a semi-solid pap (maize flour, black beans, oil) and a liquid gruel, Incaparina (maize flour, cotton seed flour, sugar), in addition to breast-milk and other home foods (group TD, n = 45 episodes) was offered for 14 d and compared to usual home feeding (group HF, n = 54 episodes). Diarrhea episodes after admission were significantly shorter for group TD (median 2. 0 d) than group HF (median 4. 4 d, p = 0. 003) after adjusting for potential confounders. Weight gains did not differ significantly between groups. We conclude that community-based dietary management of acute childhood diarrhea using energy-dense, locally available foods is feasible and may shorten diarrhea duration. This may encourage mothers to follow recommendations for continued feeding during diarrhea in developing country environments. 相似文献
97.
Age-related differences in distractibility and response to methylphenidate in monkeys 总被引:2,自引:0,他引:2
Prendergast MA; Jackson WJ; Terry AV Jr; Kille NJ; Arneric SP; Decker MW; Buccafusco JJ 《Cerebral cortex (New York, N.Y. : 1991)》1998,8(2):164-172
Increased susceptibility to distraction is a symptom of normal aging and
several clinical syndromes, including Alzheimer's disease and attention
deficit disorders. In the present study, aged and young adult macaques were
well-trained to perform an automated delayed matching-to- sample (DMTS)
task which assesses both attention and short-term memory. On 19% of all
trials, a task-relevant distracting stimulus was presented during either
the initial 1 or 3 s of delay intervals (early onset) or the final 1 or 3 s
of delay intervals (late onset). In aged monkeys, both early and late onset
distractors lasting 1 or 3 s impaired delayed recall on trials with the
shortest delay intervals, but did not affect accuracy on trials with long
delay intervals. In contrast, young adult monkeys were impaired only by the
presence of an early onset distractor lasting 3 s. Impairment was selective
for only those trials with the shortest delay intervals. Late onset
distractors were relatively ineffective in producing distractibility in
young adult animals. Methylphenidate (MPH; 0.005-1.0 mg/kg) failed to
reduce distractibility in aged monkeys, producing locomotor abnormalities
and hypophagia at doses ranging from 0.25 to 1.0 mg/kg. In young adult
monkeys, however, distractibility was significantly attenuated by
administration of the 0.125 mg/kg dose. Habituation to the distracting
stimulus (under saline conditions) was assessed throughout the study and
was not evident at any time point of testing. These data indicate that
attention and recall after brief delays are impaired following exposure to
a task-relevant distracting stimulus in both aged and young adult monkeys,
but that aged monkeys are more susceptible to distraction and do not
receive significant benefit from MPH administration.
相似文献
98.
Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans 总被引:10,自引:0,他引:10
Bellamy R; Ruwende C; McAdam KP; Thursz M; Sumiya M; Summerfield J; Gilbert SC; Corrah T; Kwiatkowski D; Whittle HC; Hill AV 《QJM : monthly journal of the Association of Physicians》1998,91(1):13-18
We retrospectively studied MBP genotypes in patients with malaria,
tuberculosis (TB), and persistent hepatitis B virus (HBV) carriage, in
clinics and hospitals in The Gambia. Children under 10 years with cerebral
malaria and/or severe malarial anaemia, were compared with children with
symptomatic, mild malaria, and controls of the same age and ethnicity.
Adult TB cases with smear-positive pulmonary TB were compared with healthy
blood donors from the same ethnic groups. Malaria cases and controls were
tested for hepatitis B core antibody (anti-HBc) and surface antigen
(HBsAg). TB patients were tested for HIV antibodies. Genotyping used
sequence-specific oligonucleotide analysis to identify MBP variant alleles.
Overall, 46% (944/2041) of patients and controls were homozygous for the
wild-type MBP allele, 45% (922/2041) were carriers of a single variant
allele and 8.6% (175/2041) had two variant alleles. Neither homozygotes nor
heterozygotes for MBP variants were at increased risk of clinical malaria,
persistent HBV carriage or TB. The most common mutation in Africans, the
codon 57 variant allele, was weakly associated with resistance to TB
(221/794 in TB cases and 276/844 in controls, p = 0.037). MBP deficiency is
not a significant risk factor for persistent HBV, severe malaria nor
pulmonary TB in West Africa.
相似文献
99.
AV Navaratnam R Ariyaratnam NJ Smart M Parker RW Motson TH Arulampalam 《Annals of the Royal College of Surgeons of England》2015,97(1):17-21
IntroductionIncisional hernia is a common complication of laparoscopic colorectal surgery. Extraction site may influence the rate of incisional hernias. Major risk factors for the development of incisional hernias include age, diabetes, obesity and smoking status. In this study, we investigated the effect of specimen extraction site on incisional hernia rate.MethodsTwo cohorts of patients who underwent laparoscopic colorectal resections in a single centre in 2005 (n=85) and 2009 (n=139) were studied retrospectively. In 2005 all specimens were extracted through transverse muscle cutting incisions. In 2009 all specimens were extracted through midline incisions. Demographic variables, rate of incisional hernias and risk factors for hernia development were compared between the year groups. All patients had been followed up clinically for two years.ResultsA total of 224 patients (mean age: 67.5 years, standard deviation: 16.35 years) were included in this study. Of these, 85 patients were in the 2005 transverse group and 139 were in the 2009 midline group. The total incisional hernia rate for the series was 8.0% at the two-year follow-up visit. For the 2005 group, the incisional hernia rate was 15.3% (n=13) and for the 2009 group, it was 3.6% (n=5) (p<0.01). The body mass index was higher in patients who developed incisional hernias than in those who did not (p=0.02).ConclusionsThe 2005 group had a significantly higher incisional hernia rate than the 2009 group. This is due to the differences in the incision technique and extraction site between the two groups. 相似文献
100.
正导读:从椅子、沙发上站起来吧!即使你经常锻炼,坐得太久也可能会危及生命。近日,来自美国癌症协会的一项研究表明,与每天坐不到3小时的人相比,如果你一天坐6个小时或者更久,过早死亡的风险会增加19%。2018年6月26日,这一成果以"Prolonged Leisur-Time Spent Sitting in Relation to Cause-specific Mortality 相似文献