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排序方式: 共有201条查询结果,搜索用时 15 毫秒
71.
72.
Gras C Amilhon B Lepicard EM Poirel O Vinatier J Herbin M Dumas S Tzavara ET Wade MR Nomikos GG Hanoun N Saurini F Kemel ML Gasnier B Giros B El Mestikawy S 《Nature neuroscience》2008,11(3):292-300
Three subtypes of vesicular transporters accumulate glutamate into synaptic vesicles to promote its vesicular release. One of the subtypes, VGLUT3, is expressed in neurons, including cholinergic striatal interneurons, that are known to release other classical transmitters. Here we showed that disruption of the Slc17a8 gene (also known as Vglut3) caused an unexpected hypocholinergic striatal phenotype. Vglut3(-/-) mice were more responsive to cocaine and less prone to haloperidol-induced catalepsy than wild-type littermates, and acetylcholine release was decreased in striatum slices lacking VGLUT3. These phenotypes were associated with a colocalization of VGLUT3 and the vesicular acetylcholine transporter (VAChT) in striatal synaptic vesicles and the loss of a synergistic effect of glutamate on vesicular acetylcholine uptake. We propose that this vesicular synergy between two transmitters is the result of the unbalanced bioenergetics of VAChT, which requires anion co-entry for continuing vesicular filling. Our study reveals a previously unknown effect of glutamate on cholinergic synapses with potential functional and pharmacological implications. 相似文献
73.
We previously reported that intracellular oxidation-reduction (redox)
regulates NK cell functions and that IL-2-activated NK cells undergo
apoptosis upon contact with NK-sensitive target cells. We now report that
apoptosis in activated human NK cells is also regulated by redox. Thiol
deprivation increased apoptosis in NK cells induced by anti-Fas mAb or Fas
ligand-transfected cells, and pretreatment of cells with N- acetyl
cysteine, which increased intracellular glutathione, partially inhibited
the apoptosis and reversed the effect of thiol-deficient medium, suggesting
that Fas-induced apoptosis in NK cells is also redox sensitive. Thiol
deprivation did not alter cell surface Fas expression, but did increase
ceramide generation following Fas engagement. Although exogenous ceramides
induced apoptosis of NK cells, thiol depletion had no effect on this
apoptosis. Thiol deprivation increased CPP32 activation induced by Fas
engagement, but not by ceramides. These findings suggest that, if ceramide
is required for Fas-induced apoptosis, thiol deprivation affects the
Fas-mediated signaling pathway at the generation of ceramide and/or
upstream thereof. Though tyrosine phosphorylation following Fas engagement
was not significantly affected by thiol deprivation, tyrosine
dephosphorylation was delayed, suggesting that tyrosine phosphatases may
also be redox sensitive. The notion that dephosphorylation is important in
the Fas signaling pathway is supported by the finding that tyrosine
phosphatase inhibitors significantly enhanced both CPP32 activity and
apoptosis following Fas ligation. We conclude that events downstream of
tyrosine phosphorylation and upstream of CPP32 activation, including
tyrosine dephosphorylation and possibly ceramide generation, are sensitive
to regulation by redox in human NK cells, requiring a reducing environment
for optimal protection from apoptosis induced by Fas ligation.
相似文献
74.
75.
应用免疫络化S-P法检测88例食管浸润世鳞癌P16蛋白的表达,结果P16蛋白阳性率为55.68%(49/88),其阳性颗粒位于细胞浆内;组织学Ⅰ、Ⅱ、Ⅲ级阳性率分予的85.71%(18/21)、55.13%(16/29)、39.47%(15/38)(P<0.01);淋巴结转移组和无转移组阳世事分别为36.36%(12/33),67.27%(37/55)(P<0.01);3年生存率P16蛋白阳性组和阴性组分别36%和16.67%。结果表明食管鳞癌中P16蛋白的表达可以反映肿瘤的分化程度和转移情况.提示P16蛋白的检测可作为食管鳞癌的重要预后指标之一。 相似文献
76.
Experiments were performed to assess the ability of bencianol (ZY15051) to reverse contractions of human basilar arteries in vitro that were induced by a wide range of substances implicated in the aetiology of migraine and cerebral arterial spasm. Bencianol caused a dose-related (1-100 micrograms ml-1) reversal of contractions induced by 5-hydroxytryptamine, noradrenaline, angiotensin II, prostaglandin F2 alpha, and U-46619 (a thromboxane-A2 mimetic). Bencianol was more effective against contractions induced by EC50 compared to maximal concentrations of each agent, and was least effective against the thromboxane-A2 mimetic, U-46619. In addition, contractions induced by thromboxane-A2-like substances generated from guinea-pig lungs were also reversed by bencianol but only at the highest concentration used (100 micrograms ml-1). The relevance of this action of bencianol to migraine and cerebral arterial spasm is discussed. 相似文献
77.
78.
Sperm nitric oxide and motility: the effects of nitric oxide synthase stimulation and inhibition 总被引:2,自引:1,他引:2
Nitric oxide (NO) is synthesized from L-arginine by a family of enzymes
known as the nitric oxide synthases (NOS). We have recently shown a NOS
similar to constitutive brain NOS (bNOS) and endothelial NOS (ecNOS) to be
present in spermatozoa. The aim of this study is to investigate NO
production by human spermatozoa and the effects of stimulation and
inhibition of NOS. This was carried out using the Iso-NO, an isolated NO
meter and sensor, which provides rapid, accurate and direct measurements of
NO. Semen samples with normozoospermic and asthenozoospermic profiles were
prepared using a direct swim-up technique. Basal concentrations of NO and
stimulated NO production were measured after exposure to the calcium
ionophore (A23187; 0.01-10 microM) a potent activator of constitutive NOS.
NO production in human spermatozoa was significantly increased by the
addition of A23187 30 seconds after stimulation. Furthermore, this response
was greatly diminished by pre-incubating the samples with competitive
inhibitors of L-arginine, the substrate for NOS, before treatment with
calcium ionophore. In the presence of N(G)-nitro-L-arginine methyl ester
(L- NAME), N(G)-nitro-L-arginine (L-NA) or N(G)-methyl-L-arginine (L-NMMA;
all at 10 microM), NO production was inhibited with a rank order of potency
L-NAME > L-NMMA > L-NA which is in accordance with the inhibition of
an endothelial type of constitutive NOS.
相似文献
79.
Daniel M Hutcheson Eleni Th. Tzavara Claire Smadja Emmanuel Valjent Bernard P Roques Jacques Hanoune Rafael Maldonado 《British journal of pharmacology》1998,125(7):1567-1577
- Tolerance and dependence induced by chronic Δ-9-tetrahydrocannabinol (THC) administration were investigated in mice. The effects on body weight, analgesia and hypothermia were measured during 6 days of treatment (10 or 20 mg kg−1 THC twice daily). A rapid tolerance to the acute effects was observed from the second THC administration.
- The selective CB-1 receptor antagonist SR 141716A (10 mg kg−1) was administered at the end of the treatment, and somatic and vegetative manifestations of abstinence were evaluated. SR 141716A administration precipitated several somatic signs that included wet dog shakes, frontpaw tremor, ataxia, hunched posture, tremor, ptosis, piloerection, decreased locomotor activity and mastication, which can be interpreted as being part of a withdrawal syndrome.
- Brains were removed immediately after the behavioural measures and assayed for adenylyl cyclase activity. An increase in basal, forskolin and calcium/calmodulin stimulated adenylyl cyclase activities was specifically observed in the cerebellum of these mice.
- The motivational effects of THC administration and withdrawal were evaluated by using the place conditioning paradigm. No conditioned change in preference to withdrawal associated environment was observed. In contrast, a conditioned place aversion was produced by the repeated pairing of THC (20 mg kg−1), without observing place preference at any of the doses used.
- This study constitutes a clear behavioural and biochemical model of physical THC withdrawal with no motivational aversive consequences. This model permits an easy quantification of THC abstinence in mice and can be useful for the elucidation of the molecular mechanisms involved in cannabinoid dependence.
80.
Abstract: Salmon I calcitonin was synthesized using both phase‐change and conventional solid‐phase fragment condensation (SPFC) approaches, utilizing the Rink amide linker (Fmoc‐amido‐2,4‐dimethoxybenzyl‐4‐phenoxyacetic acid) combined with 2‐chlorotrityl resin and the Fmoc/tBu(Trt)‐based protection scheme. Phase‐change synthesis, performed by the selective detachment of the fully protected C‐terminal 22‐mer peptide‐linker from the resin and subsequent condensation in solution with the N‐terminal 1–10 fragment, gave a product of slightly less purity (85 vs. 92%) than the corresponding synthesis on the solid‐phase. In both cases salmon I calcitonin was easily obtained in high purity. 相似文献