首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1430篇
  免费   95篇
  国内免费   69篇
耳鼻咽喉   8篇
儿科学   113篇
妇产科学   22篇
基础医学   175篇
口腔科学   110篇
临床医学   151篇
内科学   250篇
皮肤病学   23篇
神经病学   89篇
特种医学   177篇
外科学   141篇
综合类   43篇
预防医学   86篇
眼科学   32篇
药学   110篇
中国医学   6篇
肿瘤学   58篇
  2021年   29篇
  2020年   18篇
  2019年   15篇
  2018年   27篇
  2017年   20篇
  2016年   27篇
  2015年   24篇
  2014年   31篇
  2013年   36篇
  2012年   52篇
  2011年   48篇
  2010年   48篇
  2009年   43篇
  2008年   55篇
  2007年   94篇
  2006年   43篇
  2005年   32篇
  2004年   40篇
  2003年   41篇
  2002年   19篇
  2001年   36篇
  2000年   29篇
  1999年   56篇
  1998年   35篇
  1997年   41篇
  1996年   35篇
  1995年   30篇
  1994年   26篇
  1993年   27篇
  1992年   34篇
  1991年   30篇
  1990年   33篇
  1989年   39篇
  1988年   36篇
  1987年   30篇
  1986年   39篇
  1985年   26篇
  1984年   20篇
  1983年   18篇
  1982年   17篇
  1981年   11篇
  1980年   12篇
  1979年   13篇
  1978年   12篇
  1977年   16篇
  1976年   16篇
  1975年   14篇
  1974年   11篇
  1970年   12篇
  1969年   16篇
排序方式: 共有1594条查询结果,搜索用时 15 毫秒
1.
2.
Treatment of rat pheochromocytoma PC18 cells (a variant subclone of PC12 cells) with forskolin produced increased activity and phosphorylation of tyrosine hydroxylase. In contrast, treatment of the PC18 cells with 56 mM K+, A23187, phorbol-12-myristate-13-acetate (PMA) or phorbol-12,13-dibutyrate (PDB) did not affect the activity and only slightly increased the phosphorylation of tyrosine hydroxylase. None of the treatments except forskolin increased cyclic AMP levels in PC18 cells. Furthermore, 45Ca2+ uptake into PC18 cells was not affected by 56 mM K+, PDB or forskolin; however, A23187 increased 45Ca2+ uptake 4-fold over basal uptake. Nevertheless, no activation and little increase in phosphorylation of tyrosine hydroxylase was observed in PC18 cells treated with A23187. When tyrosine hydroxylase levels in PC18 cells were elevated by treatment with dexamethasone, activation of tyrosine hydroxylase by 56 mM K+, PDB or A23187 was still not observed. Both purified Ca2+/calmodulin-dependent protein kinase and cyclic AMP-dependent protein kinase catalyzed the phosphorylation of tyrosine hydroxylase purified from PC18 cells in vitro. Furthermore, crude cell extracts from PC12 cells and PC18 cells possessed Ca2+/calmodulin-dependent protein kinase activity that catalyzed the phosphorylation of purified tyrosine hydroxylase. These results suggest that tyrosine hydroxylase activity in PC18 cells is regulated by a cyclic AMP-dependent mechanism. However, due to a number of abnormalities the Ca(2+)-dependent mechanisms do not result in the activation of tyrosine hydroxylase and only slightly increase the phosphorylation of the enzyme in PC18 cells.  相似文献   
3.
OBJECTIVE: Caregivers of young children frequently measure doses of liquid medications incorrectly. Use of nonstandardized dosing instruments and lack of knowledge that dosing is weight-based contribute to dosing errors. We sought to assess whether low caregiver health literacy was associated with these outcomes. METHODS: This was a cross-sectional analysis of caregivers presenting to an urban pediatric emergency room. Dependent variables were caregiver reported use of nonstandardized dosing tools and knowledge of weight-based dosing. The independent variable was caregiver health literacy (Test of Functional Health Literacy in Adults [TOFHLA]). RESULTS: Two hundred ninety-two caregivers were assessed: 23.3% reported use of nonstandardized liquid dosing instruments, and 67.8% were unaware of weight-based dosing. Caregivers who were unaware of weight-based dosing were more likely to use nonstandardized dosing tools (28.3% vs 12.8%; P = .003). In unadjusted analyses, overall health literacy, reading comprehension, and numeracy were all associated with both dependent variables. In analyses adjusting for child age, health care experiences, and caregiver acculturation and education, inadequate/marginal overall health literacy was associated with lack of knowledge of weight-based dosing (adjusted odds ratio [AOR] 2.3; P = .03), whereas lower reading comprehension was associated with both lack of knowledge (AOR 2.0; P = .03) and reported use of nonstandardized instrument (AOR 2.4; P = .007). CONCLUSIONS: Low health literacy, in particular reading comprehension, was associated with reported use of nonstandardized dosing instruments and lack of knowledge regarding weight-based dosing. Both caregiver health literacy and sociodemographic factors should be considered in the design of interventions to prevent medication administration errors.  相似文献   
4.
A case of adenocarcinoma of a single functioning kidney is presented. The tumour was removed by extracorporeal bench surgery and the remnant successfully autotransplanted.  相似文献   
5.
6.
We studied the effect of the KATP channel blockers tolbutamide and glibenclamide on presynaptic membrane currents in the mouse M. triangularis sterni preparation using the perineural recording technique. Both sulfonylureas blocked part of the fast K+ component within 2 min after application. The block was much more pronounced under glucose-free conditions and was completelyreversible by washing. Addition of glucose to glucose-free bath solution also reduced the K+ component. A further effect of the sulfonylureas was observed under glucose-free conditions. With a delay of 5 to 10 min, the nodal Na+ component began to diminish and disappeared within 30 min. This was associated with a dramatic increase in spontaneous quantal transmitter release suggesting that the block of sulfonylurea-sensitive K+ channels causes depolarization of motor nerve terminals and fibres thus inactivating Na+ channels. Tetraethylammonium (TEA) which blocks ATP-dependent K+ channels in high concentrations caused, under glucose-free conditions, the same delayed effect as the sulfonylureas. This delayed effect was fully reversible by washing with glucose-containing, but not with glucose-free solution. Our findings strongly suggest that KATP channels exist in mammalian motor nerve endings and that under hypoglycemic conditions these channels open and become essential for the maintenance of the membrane potential.  相似文献   
7.
The mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) are important nutrient- and energy-sensing and signalling proteins in skeletal muscle. AMPK activation decreases muscle protein synthesis by inhibiting mTOR signalling to regulatory proteins associated with translation initiation and elongation. On the other hand, essential amino acids (leucine in particular) and insulin stimulate mTOR signalling and protein synthesis. We hypothesized that anabolic nutrients would be sensed by both AMPK and mTOR, resulting in an acute and potent stimulation of human skeletal muscle protein synthesis via enhanced translation initiation and elongation.
We measured muscle protein synthesis and mTOR-associated upstream and downstream signalling proteins in young male subjects ( n = 14) using stable isotopic and immunoblotting techniques. Following a first muscle biopsy, subjects in the 'Nutrition' group ingested a leucine-enriched essential amino acid–carbohydrate mixture (EAC). Subjects in the Control group did not consume nutrients. A second biopsy was obtained 1 h later. Ingestion of EAC significantly increased muscle protein synthesis, modestly reduced AMPK phosphorylation, and increased Akt/PKB (protein kinase B) and mTOR phosphorylation ( P < 0.05). mTOR signalling to its downstream effectors (S6 kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation status) was also increased ( P < 0.05). In addition, eukaryotic elongation factor 2 (eEF2) phosphorylation was significantly reduced ( P < 0.05). Protein synthesis and cell signalling (phosphorylation status) was unchanged in the control group ( P > 0.05).
We conclude that anabolic nutrients alter the phosphorylation status of both AMPK- and mTOR-associated signalling proteins in human muscle, in association with an increase in protein synthesis not only via enhanced translation initiation but also through signalling promoting translation elongation.  相似文献   
8.
The Xenopus oocyte nucleus (GV) is a storehouse for a large number of proteins that are used during early development. We have cloned and characterized a cDNA coding for a maternal gene product that is localized in the GV and then becomes highly enriched in the nuclei of the central nervous system (CNS) of tadpoles and adult frogs. This cDNA (xlgv7) is 2.1 kb and hybridizes to a 2.4-kb RNA species on Northern blots. Southern blots of genomic DNA suggest that this gene is a member of a multigene family. The cDNA sequence reveals a long open reading frame (ORF) of 1773 nucleotides, with a putative nuclear targeting signal (Glu Arg Arg Lys Lys Lys Thr) at the extreme carboxyl terminus and an internal histidine (His)-rich region with a repeated conserved amino acid sequence between His pairs. The significance of this region is unclear, but the protein is a DNA-binding protein, and it is possible that this region is involved in this function. The xlgv7 protein also possesses a putative nucleotide-binding consensus sequence that is similar to the bacterial RecA and RecB and yeast RAD proteins. Protein xlgv7 exists as several isotypes that exhibit developmental and cell-specific changes during development. Northern blot analysis of the abundance of the xlgv7 mRNA shows an accumulation following neural induction at stages 15-16. There is a transient expression of the mRNA in the gut of tadpoles. In the adult, the mRNA is highly enriched in the brain and is absent or in very low abundance in other tissues. Immunohistochemical analysis of the protein shows that the protein is localized in the nuclei of the brain cells. We conclude that the xlgv7 gene product is a maternal protein that may serve several important functions, one of which may be in the development and maintanance of the CNS.  相似文献   
9.
An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4) deficiency. Activities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively. Western blot analysis demonstrated that the amount of E3 protein in fibroblasts from the patient and her father was about half of controls, while Northern blot analysis showed normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs from the patient revealed two mutations in separate alleles. One is a single base insertion of an extra adenine in the last codon of the leader peptide sequence (TAC-->TAAC) leading to a nonsense mutation which results in the premature termination of the precursor E3 polypeptide (Y35X). The other is a missense mutation due to substitution of guanine for adenine, causing an Arg-->Gly substitution at amino acid 460 of the mature protein (R460G) which triggers the loss of E3 activity probably by structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the parents demonstrated that the nonsense mutation was inherited from the father and the missense mutation was inherited from the mother.   相似文献   
10.
Does neuroretinitis rule out multiple sclerosis?   总被引:1,自引:0,他引:1  
Neuroretinitis, a form of optic neuritis, is characterized by papillitis and a stellate macular exudate, or "macular star." The star implies the presence of a disc vasculopathy and secondary leakage of lipoproteinaceous material into the macula. Demyelinating optic neuritis would not be expected to produce a secondary macular exudate. We reviewed the literature on the risk of multiple sclerosis developing in a patient after an attack of optic neuritis, and rarely found a comment on the presence of a macular star. We then reviewed two series of 40 patients who had neuroretinitis and added ten patients of our own. Signs of multiple sclerosis had not developed in the 13 patients contacted retrospectively, nor in the patients followed up prospectively. We also noted that in our patients, neuroretinitis may be accompanied by other neurologic manifestations; neuroretinitis may be bilateral and may be staggered; papillitis may present without a macular star, only to have typical exudates develop up to two weeks later; and the macular exudate may take up to 12 months to resolve. We suggest that patients who demonstrate acute papillitis with a normal macula be reevaluated within two weeks for the development of a macular star. Its presence militates strongly against the subsequent development of multiple sclerosis.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号