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101.
102.
Sandra L. Siedlak Gemma Casadesus Kate M. Webber Miguel A. Pappolla Craig S. Atwood Mark A. Smith 《Free radical research》2013,47(2):156-164
Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, pathology and biochemistry require further clarification. To address this, young and aged control and amyloid-β protein precursor-over-expressing mice were fed a diet with added R-alpha lipoic acid for 10 months to determine the effect of chronic antioxidant administration on the cognition and neuropathology and biochemistry of the brain. Both wild type and transgenic mice treated with R-alpha lipoic acid displayed significant reductions in markers of oxidative modifications. On the other hand, R-alpha lipoic acid had little effect on Y-maze performance throughout the study and did not decrease end-point amyloid-β load. These results suggest that, despite the clear role of oxidative stress in mediating amyloid pathology and cognitive decline in ageing and AβPP-transgenic mice, long-term antioxidant therapy, at levels within tolerable nutritional guidelines and which reduce oxidative modifications, have limited benefit. 相似文献
103.
《Free radical research》2013,47(4):460-478
AbstractThis review will present a current understanding of mechanisms for the initiation of base excision repair (BER) of oxidatively-induced DNA damage and the biological consequences of deficiencies in these enzymes in mouse model systems and human populations. 相似文献
104.
《Journal of receptor and signal transduction research》2013,33(6):410-419
The α1-adrenergic receptor (AR) subtypes (α1a, α1b, and α1d) mediate several physiological effects of epinephrine and norepinephrine. Despite several studies in recombinant systems and insight from genetically modified mice, our understanding of the physiological relevance and specificity of the α1-AR subtypes is still limited. Constitutive activity and receptor oligomerization have emerged as potential features regulating receptor function. Another recent paradigm is that βarrestins and G protein-coupled receptors themselves can act as scaffolds binding a variety of proteins and this can result in growing complexity of the receptor-mediated cellular effects. The aim of this review is to summarize our current knowledge on some recently identified functional paradigms and signaling networks that might help to elucidate the functional diversity of the α1-AR subtypes in various organs. 相似文献
105.
106.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):282-289
Eighteen substituted thiophene and benzothiophene derivatives were studied for their effects on peroxisome proliferator-activated receptor γ (PPARγ) in HepG2 cells. Three derivatives (compounds 5, 120.97%; 15, 102.14%; and 17, 113.82%) were found to transactivate PPARγ in vitro. By comparison, the positive control rosiglitazone (Ros) transactivated PPARγ by 311.53%. The three compounds were studied for their effects on glucose metabolism in vivo in KK/Ay diabetic mice. In vivo, the 2-(β-carbonyl/sulfonyl) butyryl-thiophene compounds 5 and 15 significantly decreased blood glucose levels (compounds 5, to?<?15.6?mmol/L; 15, to?<?10?mmol/L), improved glucose tolerance, improved impaired pancreatic islet β-cells, and lowered serum insulin levels. 相似文献
107.
Toru Kimura Sirirat Amonpatumrat Ai Tsukada Toshiyuki Fukutomi Promsuk Jutabha Thanapol Thammapratip 《Nucleosides, nucleotides & nucleic acids》2013,32(12):1295-1301
Urate is the final metabolite of purine in humans. Renal urate handling is clinically important because under-reabsorption or underexcretion causes hypouricemia or hyperuricemia, respectively. We have identified a urate-anion exchanger, URAT1, localized at the apical side and a voltage-driven urate efflux transporter, URATv1, expressed at the basolateral side of the renal proximal tubules. URAT1 and URATv1 are vital to renal urate reabsorption because the experimental data have illustrated that functional loss of these transporter proteins affords hypouricemia. While mutations affording enhanced function via these transporter proteins on urate handling is unknown, we have constructed kidney-specific transgenic (Tg) mice for URAT1 or URATv1 to investigate this problem. In our study, each transgene was under the control of the mouse URAT1 promoter so that transgene expression was directed to the kidney. Plasma urate concentrations in URAT1 and URATv1 Tg mice were not significantly different from that in wild-type (WT) mice. Urate excretion in URAT1 Tg mice was similar to that in WT mice, while URATv1 Tg mice excreted more urate compared with WT. Our results suggest that hyperfunctioning URATv1 in the kidney can lead to increased urate reabsorption and may contribute to the development of hyperuricemia. 相似文献
108.
109.
Jin-E Zhang Dan Luo Rong-Yi Chen Yan-Ping Yang Ying Zhou Yi-Ming Fan 《Experimental Animals》2013,62(3):205-210
Qualitative measurement of the infective level is relatively difficult in experimental
vaginal candidiasis. Female BALB/c mice aged 8 to 10 weeks were randomly divided into E1,
E2 and E0 groups, which received subcutaneous injection of 0.05 mg, 0.1 mg of estradiol
benzoate or 0.1 ml soybean oil 3 days before vaginal inoculation, respectively, and
hormone treatment continued every other day thereafter. Each group was further divided
into infected and noninfected subgroups. The infected mice were inoculated intravaginally
with 10 µl (5 × 104 conidia) of Candida
albicans suspension, while the noninfected mice were inoculated with 10
µl phosphate-buffered saline. Direct microscopic examination, colony
count and vaginal histopathology including infection degree and inflammation extent were
performed at 3, 7 and 14 days post inoculation. Estrogen treatment increased the vaginal
fungal burden and extent of infection and inflammation compared with the control group,
and 0.3 mg/week estrogen generally induced more severe infection and inflammation than
0.15 mg/week estrogen did. Colony count peaked on day 3 and decreased remarkably after 7
days. Infection score increased gradually during the first 7 days and decreased on day 14,
while inflammation extent exacerbated progressively over the course of 14 days. This study
demonstrates that the modified histological scoring system might be more feasible than
colony count for evaluation of infectivity and dynamic change in experimental vaginal
candidiasis. 相似文献
110.
Yumiko Kirihara Mayumi Takechi Kaoru Kurosaki Yuta Kobayashi Tsutomu Kurosawa 《Experimental Animals》2013,62(3):173-180
The combination of ketamine and xylazine is a widely used anesthetic for laboratory
animals. However, due to an abuse problem in Japan, ketamine has been specified as a
narcotic since 2007. Instead of using ketamine, Kawai et al. reported an
injectable formula with an equivalent effect to the mixture of ketamine and xylazine
[11]. The mixture of 0.3 mg/kg body weight (b.w.)
medetomidine (Med.), 4.0 mg/kg b.w. midazoram (Mid.), and 5.0 mg/kg b.w. butorphanol
(But.) produced an anesthetic duration of around 40 min in outbred ICR mice. However, the
anesthetic effect of the mixture for inbred mice strains remains unknown. Therefore, we
examined anesthetic effects of the mixture of Med., Mid., and But. in the BALB/c and
C57BL/6J strains. After intraperitoneal injection into mice, right front paw, left hind
paw, and tail pinch reflexes as well as corneal and righting reflexes were observed. Every
5 min, we scored each reflex category as 0 for reaction or 1 for no reaction. As long as
the total score was at least 4 out of 5, we considered the mixture as putting a mouse in a
surgical anesthetic state. The mixture produced an anesthetic duration of more than 45 min
in both strains of mice. These results indicate that the mixture of Med., Mid., and But.
can be a useful and effective anesthesia for the BALB/c and C57BL/6J strains of inbred
mice as well as outbred ICR mice. 相似文献