全文获取类型
收费全文 | 4060篇 |
免费 | 307篇 |
国内免费 | 33篇 |
专业分类
耳鼻咽喉 | 11篇 |
儿科学 | 166篇 |
妇产科学 | 59篇 |
基础医学 | 497篇 |
口腔科学 | 95篇 |
临床医学 | 459篇 |
内科学 | 863篇 |
皮肤病学 | 40篇 |
神经病学 | 315篇 |
特种医学 | 348篇 |
外科学 | 480篇 |
综合类 | 128篇 |
预防医学 | 311篇 |
眼科学 | 26篇 |
药学 | 368篇 |
中国医学 | 5篇 |
肿瘤学 | 229篇 |
出版年
2022年 | 33篇 |
2021年 | 78篇 |
2020年 | 33篇 |
2019年 | 74篇 |
2018年 | 76篇 |
2017年 | 59篇 |
2016年 | 73篇 |
2015年 | 77篇 |
2014年 | 100篇 |
2013年 | 154篇 |
2012年 | 205篇 |
2011年 | 206篇 |
2010年 | 140篇 |
2009年 | 126篇 |
2008年 | 174篇 |
2007年 | 211篇 |
2006年 | 177篇 |
2005年 | 162篇 |
2004年 | 165篇 |
2003年 | 163篇 |
2002年 | 121篇 |
2001年 | 92篇 |
2000年 | 79篇 |
1999年 | 81篇 |
1998年 | 91篇 |
1997年 | 100篇 |
1996年 | 105篇 |
1995年 | 73篇 |
1994年 | 58篇 |
1993年 | 59篇 |
1992年 | 54篇 |
1991年 | 44篇 |
1990年 | 75篇 |
1989年 | 76篇 |
1988年 | 84篇 |
1987年 | 65篇 |
1986年 | 53篇 |
1985年 | 60篇 |
1984年 | 29篇 |
1983年 | 27篇 |
1982年 | 32篇 |
1981年 | 35篇 |
1980年 | 33篇 |
1979年 | 43篇 |
1978年 | 27篇 |
1977年 | 33篇 |
1976年 | 29篇 |
1973年 | 26篇 |
1972年 | 28篇 |
1971年 | 26篇 |
排序方式: 共有4400条查询结果,搜索用时 10 毫秒
31.
Kevil CG Hicks MJ He X Zhang J Ballantyne CM Raman C Schoeb TR Bullard DC 《The American journal of pathology》2004,165(2):609-616
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex-mediated tissue injury. Many different adhesion molecules are thought to participate in the development of SLE; however, few studies have directly examined the contributions of these proteins. Here we demonstrate that LFA-1 plays an essential role in the development of lupus in MRL/MpJ-Fas(lpr) mice. Mice deficient in LFA-1, but not Mac-1, showed significantly increased survival, decreased anti-DNA autoantibody formation, and reduced glomerulonephritis. The phenotype of the LFA-1-deficient mice was similar to that observed in beta(2) integrin-deficient (CD18-null) MRL/MpJ-Fas(lpr) mice, suggesting a lack of redundancy among the beta(2) integrin family members and other adhesion molecules. These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE. 相似文献
32.
The development of both adenocarcinoma of the jejunum and in situ squamous carcinoma of the oesophagus in an adult coeliac patient is described. Good evidence that adenocarcinoma of jejunum occurs more frequently in patients with coeliac disease has recently become available though this association has been suggested for some time. While oesophageal carcinoma has long been associated with coeliac disease, in situ carcinoma of oesophagus has not been previously described in these circumstances. We feel that the risk of this complication, as calculated from published series, warrants a screening programme for oesophageal malignancy in adult coeliacs. 相似文献
33.
Nano-C60 cytotoxicity is due to lipid peroxidation 总被引:20,自引:0,他引:20
This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C60, a fullerene aggregate that readily forms when pristine C60 is added to water. Nano-C60 was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses 50 ppb (LC50=2–50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C60 colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C60 inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, l-ascorbic acid, the oxidative damage and resultant toxicity of nano-C60 was completely prevented. 相似文献
34.
Factors affecting the determination of threshold doses for allergenic foods: how much is too much? 总被引:15,自引:0,他引:15
Steve L Taylor Susan L Hefle Carsten Bindslev-Jensen S Allan Bock A Wesley Burks Lynn Christie David J Hill Arne Host Jonathan O'b Hourihane Gideon Lack Dean D Metcalfe Denise Anne Moneret-Vautrin Peter A Vadas Fabienne Rance Daniel J Skrypec Thomas A Trautman Ingrid Malmheden Yman Robert S Zeiger 《The Journal of allergy and clinical immunology》2002,109(1):24-30
BACKGROUND: Ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies. The threshold dose for provocation of such reactions is often considered to be zero. However, because of various practical limitations in food production and processing, foods may occasionally contain trace residues of the offending food. Are these very low, residual quantities hazardous to allergic consumers? How much of the offending food is too much? Very little quantitative information exists to allow any risk assessments to be conducted by the food industry. OBJECTIVE: We sought to determine whether the quality and quantity of existing clinical data on threshold doses for commonly allergenic foods were sufficient to allow consensus to be reached on establishment of threshold doses for specific foods. METHODS: In September 1999, 12 clinical allergists and other interested parties were invited to participate in a roundtable conference to share existing data on threshold doses and to discuss clinical approaches that would allow the acquisition of that information. RESULTS: Considerable data were identified in clinical files relating to the threshold doses for peanut, cows' milk, and egg; limited data were available for other foods, such as fish and mustard. CONCLUSIONS: Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed. 相似文献
35.
Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease 总被引:5,自引:2,他引:5
The allelic frequency of the gene for the K variant of
butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age
> 65 years) histopathologically diagnosed Alzheimer's disease (AD),
which was higher than the frequencies in 104 elderly control subjects
(0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed
cases of other dementia (0.10). The association of BCHE-K with late-onset
AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E
gene (APOE), among whom the presence of BCHE-K gave an odds ratio of
confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years
and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers
over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset
AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on
chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene
for late-onset AD.
相似文献
36.
37.
Muda M He C Martini PG Ferraro T Layfield S Taylor D Chevrier C Schweickhardt R Kelton C Ryan PL Bathgate RA 《Molecular human reproduction》2005,11(8):591-600
LGR7 and LGR8 are G protein-coupled receptors that belong to the leucine-rich repeat-containing G-protein coupled receptor (LGR) family, including the thyroid-stimulating hormone (TSH), LH and FSH receptors. LGR7 and LGR8 stimulate cAMP production upon binding of the cognate ligands, relaxin and insulin-like peptide 3 (INSL3), respectively. We cloned several novel splice variants of both LGR7 and LGR8 and analysed the function of four variants. LGR7.1 is a truncated receptor, including only the N-terminal region of the receptor and two leucine rich repeats. In contrast, LGR7.2, LGR7.10 and LGR 8.1 all contain an intact seven transmembrane domain and most of the extracellular region, lacking only one or two exons in the ectodomain. Our analysis demonstrates that although LGR7.10 and LGR8.1 are expressed at the cell surface, LGR7.2 is predominantly retained within cells and LGR7.1 is partially secreted. mRNA expression analysis revealed that several variants are co-expressed in various tissues. None of these variants were able to stimulate cAMP production following relaxin or INSL3 treatment. Unexpectedly, we did not detect any direct specific relaxin or INSL3 binding on any of the splice variants. The large number of receptor splice variants identified suggests an unforeseen complexity in the physiology of this novel hormone-receptor system. 相似文献
38.
A 50-kDa membrane protein mediates sialic acid-independent binding and infection of conjunctival cells by adenovirus type 37 总被引:6,自引:0,他引:6
The ocular tropism of adenovirus type 37 (Ad37) does not correlate with the wide distribution of the 46-kDa coxsackievirus and adenovirus receptor (CAR), the major receptor for most adenovirus serotypes. We previously found that Ad37 infects and binds well to conjunctival cells (Chang C), but poorly to lung epithelial (A549) cells that express CAR and hypothesized that this serotype uses a distinct receptor that is selectively expressed on conjunctival cells. To test this, we produced particles of a fiber-deleted Ad5 vector containing the Ad37 fiber protein. The "pseudotyped" vector infected Chang C cells better than A549 cells using a CAR-independent pathway. Ad37 binding was calcium-dependent and was abolished by protease digestion of cell surface proteins. Using a virus overlay protein blot assay (VOPBA), we detected calcium-dependent Ad37 binding to 50- and 60-kDa membrane proteins on permissive Chang C cells. In contrast, calcium-dependent binding was detected with only the 60-kDa protein on nonpermissive A549 cells. Ad19p, a closely related serotype that failed to bind to conjunctival cells, recognized the 60-kDa, but not the 50-kDa, protein. Ad37 has been reported to use sialic acid instead of CAR as a cell receptor on A549 cells. Pretreatment of Chang C cells with neuraminidase abolished Ad37 binding to only the 60-kDa protein, suggesting that sialic acid mediates Ad37 binding to the 60-kDa protein. The pseudotyped Ad37 vector was also able to infect neuraminidase-treated Chang C cells. Thus, subgroup D adenoviral binding to the 50-kDa protein is calcium-dependent and cell type- and serotype-specific, whereas binding to the 60-kDa protein is not necessary for infection of conjunctival cells. Together, these data suggest that the 50-kDa protein is the major receptor for Ad37 on conjunctival cells. 相似文献
39.
40.
Sensitization potentiates excitability in an interneuron, the S-cell, that is critical for this form of learning in the whole-body shortening reflex of the medicinal leech. Serotonin (5-HT) also increases S-cell excitability, and serotonergic modulation is known to be critical for sensitization of whole-body shortening, suggesting that 5-HT mediates learning-induced enhancement of S-cell excitability. In this paper, the role of 5-HT in mediating sensitization-induced potentiation of S-cell excitability was examined. Potentiation of S-cell excitability by 5-HT was blocked by the 5-HT receptor antagonist methysergide and by intracellular injection of the G-protein inhibitor GDP-beta-S, indicating that a metabotropic 5-HT receptor was involved. Bath application of Rp-cAMP, an inhibitor of protein kinase A (PKA), blocked 5-HT-induced potentiation of excitability, whereas db-cAMP, a cAMP analogue that activates PKA, mimicked the potentiating effects of 5-HT on the S-cell. During sensitization of the shortening reflex in semi-intact preparations, methysergide and Rp-cAMP prevented learning-induced potentiation of S-cell excitability, as well as the increase in S-cell activity that normally occurs during sensitization. Furthermore, sensitization-induced increases in the shortening reflex did not occur in preparations treated with methysergide or Rp-cAMP. These results demonstrate that sensitization-induced enhancement of S-cell excitability is mediated by 5-HT and suggests that these changes may contribute to this form of learning. 相似文献