全文获取类型
收费全文 | 19869篇 |
免费 | 1046篇 |
国内免费 | 99篇 |
专业分类
耳鼻咽喉 | 233篇 |
儿科学 | 452篇 |
妇产科学 | 296篇 |
基础医学 | 2490篇 |
口腔科学 | 570篇 |
临床医学 | 1406篇 |
内科学 | 5463篇 |
皮肤病学 | 410篇 |
神经病学 | 1690篇 |
特种医学 | 364篇 |
外科学 | 2985篇 |
综合类 | 131篇 |
一般理论 | 6篇 |
预防医学 | 1579篇 |
眼科学 | 501篇 |
药学 | 1114篇 |
1篇 | |
中国医学 | 55篇 |
肿瘤学 | 1268篇 |
出版年
2024年 | 14篇 |
2023年 | 147篇 |
2022年 | 390篇 |
2021年 | 733篇 |
2020年 | 339篇 |
2019年 | 634篇 |
2018年 | 747篇 |
2017年 | 417篇 |
2016年 | 458篇 |
2015年 | 574篇 |
2014年 | 728篇 |
2013年 | 950篇 |
2012年 | 1585篇 |
2011年 | 1669篇 |
2010年 | 897篇 |
2009年 | 855篇 |
2008年 | 1342篇 |
2007年 | 1337篇 |
2006年 | 1268篇 |
2005年 | 1203篇 |
2004年 | 1056篇 |
2003年 | 938篇 |
2002年 | 817篇 |
2001年 | 204篇 |
2000年 | 186篇 |
1999年 | 192篇 |
1998年 | 156篇 |
1997年 | 142篇 |
1996年 | 104篇 |
1995年 | 86篇 |
1994年 | 87篇 |
1993年 | 66篇 |
1992年 | 87篇 |
1991年 | 88篇 |
1990年 | 66篇 |
1989年 | 36篇 |
1988年 | 37篇 |
1987年 | 36篇 |
1986年 | 38篇 |
1985年 | 31篇 |
1984年 | 34篇 |
1983年 | 20篇 |
1982年 | 34篇 |
1981年 | 27篇 |
1980年 | 17篇 |
1978年 | 11篇 |
1977年 | 12篇 |
1976年 | 10篇 |
1974年 | 26篇 |
1973年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
101.
Summary The phenotypically wild strain I3 of Chlamydomonas reinhardtii, carrying a cryptic mutation at the nit-6 locus, was distinguished from strains 21gr (cryptic mutant at nit-5) and 6145c (wild type) because of the ability of I3 to grow on nitrate media containing 2mM tungstate.Molybdopterin-cofactor (MoCo) mutants 102 (double mutant at nit-5 and nit-6) and 104 (mutant at nit-4) grew on nitrate media supplemented with high concentrations of molybdate, although final cell densities were 40–60% lower and generation times 3.5 to six fold longer than for wild type. Under these conditions, nitrate reductase (NR) activity of the mutants, when measured either in situ or in vitro, was practically undetectable. The MoCo defective mutant 307 (nit-3) was not molybdate repairable. Although NR activity was not restored in vitro by molybdate in any of the MoCo– mutant strains, their extracts had free NR-diaphorase subunits together with NR-subunits assembled into high molecular weight species.Our results indicate that: a) nit-4, nit-5 and nit-6 loci are responsible for molybdate processing in the cell; b) nit-3 may encode a component of the pterin moiety biosynthetic route; c) NR subunits can assemble in the presence of an inactive MoCo; d) high concentrations of molybdate can replace partially in vivo but not in vitro the function of nit-4 and the combined function(s) of the nit-5 and nit-6 gene products. 相似文献
102.
García-González M Abdulkader I Boquete AV Neo XM Forteza J Cameselle-Teijeiro J 《Virchows Archiv : an international journal of pathology》2005,447(1):12-17
This study was undertaken to investigate cyclooxygenase-2 (COX-2) expression in follicular cells of the human thyroid. COX-2 expression was studied immunohistochemically in a total of 174 samples. COX-2 immunoreactivity was confined to the cell cytoplasm with the nuclei remaining unlabelled. COX-2 expression was observed in five cases (17.2%) of normal follicular cells and in one case (16.6%) of solid cell nests. Follicular carcinoma expressed COX-2 more frequently than follicular adenoma (93.4% vs 21.1%) (p0.001). A higher percentage of cases of papillary microcarcinomas up-regulated COX-2 in comparison with all papillary carcinomas (p0.05). However, we could not establish any relationships among COX-2, patients ages or lymph node metastases in papillary carcinomas. COX-2 expression was found in 12 (92.3%) poorly differentiated carcinomas and in 13 (92.8%) undifferentiated carcinomas. We found that COX-2 is not always useful as a marker of malignancy. Our results suggest that COX-2 plays a role in progression of all thyroid carcinomas, but in papillary carcinomas, seems more important only in the early stages. COX-2 expression in the undifferentiated carcinoma deserves special consideration due to its prognosis and to the fact that selective COX-2 inhibitors were found to enhance tumour response to radiation in some studies. 相似文献
103.
Sala F Mulet J Reddy KP Bernal JA Wikman P Valor LM Peters L König GM Criado M Sala S 《Neuroscience letters》2005,373(2):144-149
The effects of various Flustra foliacea metabolites on different types of human neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated. Whereas most of the compounds tested had a small blocking effect, one of them, deformylflustrabromine, selectively increased the current obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The current increase was reversible and concentration-dependent. This potentiating effect was still present at saturating concentrations of acetylcholine, and no changes in single-channel conductance or reversal potential were observed, thus suggesting a modification in the gating of alpha4beta2 receptors. Dwell time analysis of single channel records indicates that the mechanism of action of deformylflustrabromine could be both an increase of the opening rate constant and a decrease of the closing rate constant on alpha4beta2 receptors. Thus, deformylflustrabromine may constitute an excellent starting point for the future development of related agents able to potentiate human neuronal nicotinic receptor function. 相似文献
104.
Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy 总被引:4,自引:0,他引:4
Chan EM Ackerley CA Lohi H Ianzano L Cortez MA Shannon P Scherer SW Minassian BA 《Human molecular genetics》2004,13(11):1117-1129
Lafora disease (LD) is a fatal and the most common form of adolescent-onset progressive epilepsy. Fulminant endoplasmic reticulum (ER)-associated depositions of starch-like long-stranded, poorly branched glycogen molecules [known as polyglucosans, which accumulate to form Lafora bodies (LBs)] are seen in neuronal perikarya and dendrites, liver, skeletal muscle and heart. The disease is caused by loss of function of the laforin dual-specificity phosphatase or the malin E3 ubiquitin ligase. Towards understanding the pathogenesis of polyglucosans in LD, we generated a transgenic mouse overexpressing inactivated laforin to trap normal laforin's unknown substrate. The trap was successful and LBs formed in liver, muscle, neuronal perikarya and dendrites. Using immunogold electron microscopy, we show that laforin is found in close proximity to the ER surrounding the polyglucosan accumulations. In neurons, it compartmentalizes to perikaryon and dendrites and not to axons. Importantly, it binds polyglucosans, establishing for the first time a direct association between the disease-defining storage product and disease protein. It preferentially binds polyglucosans over glycogen in vivo and starch over glycogen in vitro, suggesting that laforin's role begins after the appearance of polyglucosans and that the laforin pathway is involved in monitoring for and then preventing the formation of polyglucosans. In addition, we show that the laforin interacting protein, EPM2AIP1, also localizes on the polyglucosan masses, and we confirm laforin's intense binding to LBs in human LD biopsy material. 相似文献
105.
Concepción Núñez Diana Alecsandru Jezabel Varadé Isabel Polanco Carlos Maluenda Miguel Fernández-Arquero Emilio G de la Concha Elena Urcelay Alfonso Martínez 《BMC medical genetics》2006,7(1):32-5
Background
Celiac disease (CD) is a chronic disorder characterized by a pathological inflammatory response after exposure to gluten in genetically susceptible individuals. The HLA complex accounts for less than half of the genetic component of the disease, and additional genes must be implicated. Interleukin-10 (IL-10) is an important regulator of mucosal immunity, and several reports have described alterations of IL-10 levels in celiac patients. The IL-10 gene is located on chromosome 1, and its promoter carries several single nucleotide polymorphisms (SNPs) and microsatellites which have been associated to production levels. Our aim was to study the role of those polymorphisms in susceptibility to CD in our population. 相似文献106.
107.
108.
109.
Pkd2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cells 总被引:7,自引:0,他引:7
Qian Q Hunter LW Li M Marin-Padilla M Prakash YS Somlo S Harris PC Torres VE Sieck GC 《Human molecular genetics》2003,12(15):1875-1880
Autosomal-dominant polycystic kidney disease is a multiorgan disease and its vascular manifestations are common and life-threatening. Despite this, little is known about their pathogenesis. Somatic mutations to the normal PKD allele in cystic epithelia and cyst development associated with the unstable Pkd2(WS25) allele suggest a two-hit model of cystogenesis. However, it is unclear if this model can account for the cardiovascular pathology or if haploinsufficiency alone is disease-associated. In the present study, we found a decreased polycystin-2 (PC2, protein encoded by Pkd2 gene) expression in Pkd2( +/-) vessels, roughly half the wild-type level, and an enhanced level of intracranial vascular abnormalities in Pkd2 (+/-) mice when induced to develop hypertension. Consistent with these observations, freshly dissociated Pkd2 (+/-) vascular smooth muscle cells have significantly altered intracellular Ca(2+) homeostasis. The resting [Ca(2+)](i) is 17.1% lower in Pkd2 (+/-) compared with wild-type cells (P=0.0003) and the total sarcoplasmic reticulum Ca(2+) store (emptied by caffeine plus thapsigargin) is decreased (P<0.0001). The store operated Ca(2+) (SOC) channel activity is also decreased in Pkd2 (+/-) cells (P=0.008). These results indicate that inactivation of just one Pkd2 allele is sufficient to significantly alter intracellular Ca(2+) homeostasis, and that PC2 is necessary to maintain normal SOC activity and the SR Ca(2+) store in VSMCs. Based on these findings, and the fact that [Ca(2+)](i) signaling is essential to the regulation of contraction, production and secretion of extracellular matrix, cellular proliferation and apoptosis, we propose that the abnormal intracellular Ca(2+) regulation associated with Pkd2 haploinsufficiency is directly related to the vascular phenotype. 相似文献
110.
Reza-Albarran AA Gomez-Perez FJ Lopez JC Herrera M Gamboa-Dominguez A Keirns C Aranda A Rull JA 《Endocrine pathology》1999,10(3):251-257
Pigmented nodular cortical hyperplasia, a rare cause of Cushing’s syndrome, is characterized by resistance to inhibition with
dexamethasone and normal sized adrenal glands with multiple, small pigmented nodules. The disorder may be a component of a
syndrome inherited as an autosomal dominant pattern that includes intra- and extracardiac myxomas, lentiginous lesions, blue
nevi, other functional endocrine tumors, and peripheral nerve tumors (Carney’s complex).
We report a patient in whom bilateral myelolipomas were found, in addition to the usual features of this complex. A 29-yr-old
man was admitted to the hospital for Cushing’s syndrome of probably more than 15 yr duration. Physical examination showed
diffuse facial hyperchromatic macules, 0.2–0.5 cm, predominantly around the lips and on the palmar surfaces of the fingers.
Results with dexamethasone suppression nocturnal testing (1 and 8 mg) were compatible with an adrenal adenoma. The computed
tomography (CT) of the sella turcica was normal. Adrenal CT showed a tumor in the left gland with a double component: one
solid and another suggestive of fat, consistent with an angiomyelolipoma. Following 5 wk treatment with ketoconazole, 800
mg per day po, serum cortisol decreased to 5.9 μg/dL, morning and evening, respectively.
Bilateral adrenalectomy was performed. Pathologic examination revealed pigmented nodular cortical hypersplasia and a dominant
myelolipoma in the left adrenal. A microscopic myelolipoma was identified in the right adrenal.
An echocardiogram showed a mass on the posterior wall of the left ventricle which was a myxoma. Study of the patient's family
disclosed two sisters with facial lentigines. Echocardiograms were performed on all available first degree relatives: all
were normal. Nocturnal inhibition with dexamethasone revealed that one of the patient’s sisters with lentigines also had hypercortisolism.
Myelolipoma has been reported in association to Cushing syndrome in humans and experimentally after pituitary extracts in
animals. The relationship between this finding and the Carney’s complex remain elusive. 相似文献