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排序方式: 共有431条查询结果,搜索用时 31 毫秒
1.
可逆性胆硷酯酶抑制剂二甲氨基甲酸-5-二氢吲哚酯的合成 总被引:1,自引:0,他引:1
为了深入研究催醒宁类化合物的结构与抑酶活性的关系,设计合成了-系列1-,3-或5-位不同取代的二氢吲哚类衍生物(中间体和终产物共24个新化合物)。中间体1,3-二甲基-5-烷氧基-2-二氢吲哚酮(A)的C3烷化。采用相转移催化方法进行;反应中还分离到三个副产物(Ⅶ~Ⅸ)。初筛结果表明:这些化合物大多有较强的抑酶活性;1,3-或5-位取代基的改变均明显影响其活性。 相似文献
2.
Braffman BH; Coleman BG; Ramchandani P; Arger PH; Nodine CF; Dinsmore BJ; Louie A; Betsch SE 《Radiology》1994,190(3):797
3.
Septicemia due to DF-2. Cause of a false-positive cryptococcal latex agglutination result 总被引:6,自引:0,他引:6
M A Westerink D Amsterdam R J Petell M N Stram M A Apicella 《The American journal of medicine》1987,83(1):155-158
A previously healthy 26-year-old man presented with fever, headache, skin rash, and thrombocytopenia. Cultures of blood and cerebrospinal fluid yielded a fastidious gram-negative bacillus, identified as DF-2. A unique feature of this case was the presence of a false-positive latex agglutination result for cryptococcal antigen in the cerebrospinal fluid in the absence of pleocytosis. Additional laboratory studies, which included indirect immunofluorescence and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, however, failed to reveal common antigenic surface components between these organisms. 相似文献
4.
Brain microdialysis was used to investigate whether different calcium concentrations (1.2 and 3.4 mmol/l) of the perfusion fluid influenced the effects of D2 agonists on the release of dopamine in the striatum. We used the D2 agonists (-)N-0437 and (+)PHNO. After both local and systemic administration of (-)N-0437 and (+)PHNO, differences were apparent between their effects at 1.2 mmol/l calcium and 3.4 mmol/l calcium Ringer's solution. Although the drugs induced a similar maximal decrease in the release of dopamine with both calcium concentrations, the potency of the effect was significantly greater at 1.2 mmol/l when compared to 3.4 mmol/l calcium Ringer's solution. Thus, when measuring pharmacological effects of dopaminergic agents, it seems essential to use a Ringer's solution containing the physiological calcium concentration in brain microdialysis. 相似文献
5.
The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA j(vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4–6-fold increase in the extracellular content of GABA. This increase lasted for at least 72 h. PTZ-induced convulsions were partly antagonized by the GVG treatment. The increase of extracellular GABA after gamma-vinyl-GABA was not affected by infusion of tetrodotoxin. In contrast valproic acid (200 mg/kg), although effective in preventing pentylenetetrazol (PTZ)-induced convulsions, did not affect extracellular GABA in the SNR. PTZ-induced convulsions did not modify extracellular GABA, neither in control rats nor in valproic acid or gamma-vinyl-GABA pretreated animals. The results do not support the idea that extracellular GABA in the SNR plays a significant role in anti-convulsive treatment. However, the present data can also be interpreted that extracellular GABA, as sampled by microdialysis, is not a reliable marker for GABA release. 相似文献
6.
This study was designed to determine whether the somatostatin analogue,
octreotide, could prevent embryonic loss by normalizing increased uterine
insulin-like growth factor-I (IGF-I) action related to hyperoestrogenaemia
following superovulation. Superovulated immature and
oestradiol-17beta-treated adult rats were infused with 100 or 300 microg/ml
of octreotide respectively, or injected daily with 1 or 10 microg of
octreotide from day 1 to day 3 of pregnancy. On day 3, embryos were
collected from the oviducts and uteri. Uterine luminal fluid was subjected
to embryo culture. The amounts of uterine IGF-I and IGF binding proteins
(IGFBP) were determined by radioimmunoassay and ligand binding assay
respectively. Octreotide infusion normalized uterine IGF-I action following
superovulatory and oestradiol-17beta treatment, by reducing IGF-I
concentrations and increasing IGFBP concentrations. Octreotide infusion
increased the number of normal embryos by 2.7-fold and 1.7-fold in
superovulated and oestradiol-17beta- treated rats respectively, and
reversed the detrimental effects of uterine luminal fluid on embryonic
development caused by superovulatory and oestradiol-17beta treatment. Daily
injections with octreotide had similar but reduced effects in all
parameters examined in both treatment groups. In conclusion, octreotide may
reduce embryonic loss, at least in part, by normalizing IGF-I action
following superovulation.
相似文献
7.
W. Timmerman M. Heijmen B. H. C. Westerink R. Bruggeman J. A. den Boer 《Psychopharmacology》1999,144(3):286-294
Rationale: Previously, we have shown that the atypical antipsychotics clozapine and risperidone, unlike haloperidol, decreased the
firing rate of substantia nigra reticulata (SNR) neurons. As the SNR receives substantial input from the striatum, an area
where motoric side-effects of antipsychotics are thought to be mediated, the SNR might be an interesting brain structure with
regard to motor side-effects. Objective: The newly developed atypical antipsychotic olanzapine was studied for its effects on the firing rate of SNR cells. In addition,
to gain insight in the implications of our experimental setup for clinical use, responses upon clozapine, olanzapine and haloperidol
were studied after chronic treatment. Methods: In chloralhydrate-anaesthetized male Wistar rats, extracellular recordings were made from SNR neurons upon intravenously
(IV) administered cumulative doses of the antipsychotics. Naive rats and rats that were subcutaneously (SC) injected for 21
days with an antipsychotic were used. Results: Olanzapine (50–1600 mg/kg; IV), significantly inhibited the firing rate of the SNR neurons. Upon 21 days of treatment with
a daily SC injection of 20 mg/kg clozapine, the challenge on day 22 with cumulative injections of clozapine (200–6400 mg/kg;
IV) significantly inhibited the firing rate of the SNR neurons. Olanzapine (50–1600 mg/kg; IV) also significantly inhibited
the SNR activity when pretreated with olanzapine in an SC administered dose of 1 mg/kg, but not 5 mg/kg. Haloperidol (12.5–800 μg/kg;
IV) did not significantly affect the SNR activity in rats pretreated with SC administered 0.5 mg/kg haloperidol. Conclusions: Upon acute and chronic administration of clozapine and olanzapine versus haloperidol, differential effects on SNR neuronal
firing could be obtained. The experimental setup seem to be valid for further studies into the mechanism of action of typical
versus (relatively low doses of) atypical antipsychotics. The implications of the inhibitory effect of atypical antipsychotics
on the SNR firing rate are presently unknown, but could be associated with the lower propensity to induced motoric side-effects.
On the other hand, the SNR activity might also reflect non-motoric activity possibly related to negative symptoms.
Received: 11 December 1998/Final version: 20 January 1999 相似文献
8.
S Bydder NA Spry DRH Christie D Roos BH Burmeister H Krawitz S Davis DJ Joseph M Poulsen M Berry 《Journal of Medical Imaging and Radiation Oncology》2003,47(3):284-288
The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty‐eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty‐two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high‐dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53?66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well‐tolerated treatment achieves useful palliation. 相似文献
9.
Hester S. Hendriks Marieke Meijer Mirthe Muilwijk Martin van den Berg Remco H. S. Westerink 《Archives of toxicology》2014,88(4):857-869
Brominated flame retardants (BFRs) are abundant persistent organic pollutants with well-studied toxicity. The toxicological and ecological concerns associated with BFRs argue for replacement by safe(r) alternatives. Though previous research identified the nervous system as a sensitive target organ for BFRs, the (neuro) toxic potential of alternative halogen-free flame retardants (HFFRs) is largely unknown. We therefore investigated the in vitro (neuro) toxicity of 13 HFFRs and three BFRs in dopaminergic pheochromocytoma (PC12) and neuroblastoma (B35) cells by assessing several cytotoxic and neurotoxic endpoints. Effects on cell viability and production of reactive oxygen species (ROS) were measured using a combined Alamar Blue and Neutral Red assay and a H2-DCFDA assay, respectively, whereas effects on calcium homeostasis were measured using single-cell fluorescent Ca2+-imaging. The majority of the tested flame retardants induced negligible cytotoxicity, except zinc hydroxystannate (ZHS) and zinc stannate (ZS). A considerable fraction of flame retardants affected ROS production (decabromodiphenyl ether (BDE-209), triphenylphosphate (TPP), aluminium trihydroxide (ATH), ammonium polyphosphate (APP), magnesium hydroxide (MHO), ZHS, ZS and melamine polyphosphate (MPP)). Interestingly, ATH, ZHS, ZS and montmorillonite (MMT) increased the basal intracellular calcium concentration ([Ca2+]i), whereas tetrabromobisphenol A (TBBPA), resorcinol bis (diphenylphosphate) (RDP), TPP, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), ATH, ZHS, ZS and MMT reduced depolarization-evoked increases in [Ca2+]i as a result of inhibition of voltage-gated calcium channels. These combined data on the in vitro (neuro) toxicity of HFFRs in comparison with BFRs are essential for prioritization of safe(r) flame retardants. Though additional data are required for a complete (toxic) risk assessment, our data demonstrate that several HFFRs could be suitable substitutes for BFRs. 相似文献
10.
In the human erythrocyte membrane phosphatidylcholine and sphingomyelin reside mainly in the outer leaflet, whereas the aminophospholipids, phosphatidylethanolamine and phosphatidylserine, are mainly found in the inner leaflet. Maintenance of phospholipid asymmetry has been assumed to involve interactions between the aminophospholipids and the membrane skeleton, in particular spectrin. To investigate whether spectrin contributes to maintaining the phospholipid transbilayer distribution and kinetics of redistribution, we studied erythrocytes from hereditary spherocytosis patients whose spectrin levels ranged from 34% to 82% of normal. The phospholipid composition and the accessibility of membrane phospholipids to hydrolysis by phospholipases were in the normal range. Spin-labeled phosphatidylserine and phosphatidylethanolamine analogues that had been introduced into the outer leaflet were rapidly transported at 37 degrees C to the inner leaflet, whereas the redistribution of spin-labeled phosphatidylcholine was slower. The kinetics of transbilayer movement of these spin-labeled phospholipid in all samples was in the normal range and was not affected by the level of spectrin. Although these erythrocyte membranes contained as little as 34% of the normal level of spectrin and were characterized by several physical abnormalities, the composition, distribution, and transbilayer kinetics of the phospholipids were found to be normal. We therefore conclude that spectrin plays, at best, only a minor role in maintaining the distribution of erythrocyte membrane phospholipid. 相似文献