全文获取类型
收费全文 | 233235篇 |
免费 | 11028篇 |
国内免费 | 391篇 |
专业分类
耳鼻咽喉 | 3046篇 |
儿科学 | 7269篇 |
妇产科学 | 4733篇 |
基础医学 | 33509篇 |
口腔科学 | 5306篇 |
临床医学 | 18401篇 |
内科学 | 51547篇 |
皮肤病学 | 6209篇 |
神经病学 | 20782篇 |
特种医学 | 6994篇 |
外国民族医学 | 101篇 |
外科学 | 28900篇 |
综合类 | 975篇 |
一般理论 | 62篇 |
预防医学 | 21228篇 |
眼科学 | 4553篇 |
药学 | 16376篇 |
中国医学 | 699篇 |
肿瘤学 | 13964篇 |
出版年
2023年 | 1239篇 |
2022年 | 845篇 |
2021年 | 3429篇 |
2020年 | 2036篇 |
2019年 | 3864篇 |
2018年 | 7420篇 |
2017年 | 4868篇 |
2016年 | 4855篇 |
2015年 | 5434篇 |
2014年 | 5645篇 |
2013年 | 9145篇 |
2012年 | 15970篇 |
2011年 | 15911篇 |
2010年 | 7900篇 |
2009年 | 5872篇 |
2008年 | 13681篇 |
2007年 | 14661篇 |
2006年 | 13493篇 |
2005年 | 13354篇 |
2004年 | 12529篇 |
2003年 | 11435篇 |
2002年 | 10827篇 |
2001年 | 6113篇 |
2000年 | 6214篇 |
1999年 | 5512篇 |
1998年 | 883篇 |
1997年 | 731篇 |
1996年 | 700篇 |
1992年 | 3194篇 |
1991年 | 2864篇 |
1990年 | 2732篇 |
1989年 | 2492篇 |
1988年 | 2363篇 |
1987年 | 2193篇 |
1986年 | 2087篇 |
1985年 | 1882篇 |
1984年 | 1395篇 |
1983年 | 1186篇 |
1982年 | 668篇 |
1979年 | 1203篇 |
1978年 | 845篇 |
1977年 | 795篇 |
1975年 | 800篇 |
1974年 | 984篇 |
1973年 | 994篇 |
1972年 | 935篇 |
1971年 | 922篇 |
1970年 | 860篇 |
1969年 | 905篇 |
1968年 | 787篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
941.
Seyrantepe V Poupetova H Froissart R Zabot MT Maire I Pshezhetsky AV 《Human mutation》2003,22(5):343-352
Lysosomal sialidase (EC 3.2.1.18) has a dual physiological function; it participates in intralysosomal catabolism of sialylated glycoconjugates and is involved in cellular immune response. Mutations in the sialidase gene NEU1, located on chromosome 6p21.3, result in autosomal recessive disorder, sialidosis, which is characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides. Sialidosis type I is a milder, late-onset, normosomatic form of the disorder. Type I patients develop visual defects, myoclonus syndrome, cherry-red macular spots, ataxia, hyperreflexia, and seizures. The severe early-onset form, sialidosis type II, is also associated with dysostosis multiplex, Hurler-like phenotype, mental retardation, and hepatosplenomegaly. We summarize information on the 34 unique mutations determined so far in the sialidase gene, including four novel missense and one novel nonsense mutations found in two Czech and two French sialidosis patients. The analysis of sialidase mutations in sialidosis revealed considerable molecular heterogeneity, reflecting the diversity of clinical phenotypes that make molecular diagnosis difficult. The majority of sialidosis patients have had missense mutations, many of which have been expressed; their effects on activity, stability, intracellular localization, and supramolecular organization of sialidase were studied. A structural model of sialidase allowed us to localize mutations in the sialidase molecule and to predict their impact on the tertiary structure and biochemical properties of the enzyme. 相似文献
942.
Inogés S Merino J Bandrés E De Castro P Subirá ML Sánchez-Ibarrola A 《Clinical and experimental immunology》1999,115(3):521-525
In this study we have examined intracellular cytokines in peripheral blood mononuclear cells (PBMC) of MS patients by flow cytometry (cytokine flow cytometry). MS progressive patients showed an increased number of cells producing interferon-gamma (IFN-gamma) after activation with phorbol 12-myristate 13-acetate and ionomycin, compared with patients with clinically inactive forms (P < 0001) and with healthy controls (P = 0001). These cells belonged to the CD4+ and CD8+ subsets in similar proportions. Clinically inactive patients showed a lower level of cells producing IL-2 than controls (P = 0.03) and active MS patients (P = 0.03). Most IL-2-producing cells were CD4+ lymphocytes, although a small part of the IL-2 was also produced by CD8+ cells. The percentage of cells producing simultaneously IL-2 and IFN-gamma was increased in active MS and they were mainly CD4+ lymphocytes. No differences in the production of IL-4 were observed between groups. However, we found an increased IL-10 production in clinically active MS patients (P = 0.03). Treatment with IFN-beta of active MS patients showed lower levels of cytokines when compared with untreated MS patients. This methodological approach could help in the follow up and therapeutic monitoring of MS patients. 相似文献
943.
The present study aimed at investigating the spatial variability of skin temperature (T
sk) measured at various points on the hand during convective and cold contact exposure. A group of 8 subjects participated in a study of convective cooling of the hand (60 min) and 20 subjects to contact cooling of the finger pad (5 min). Experiments were carried out in a small climatic chamber into which the hand was inserted. For convective cold exposure,T
sk was measured at seven points on the palmar surface of the fingers of the left hand, one on the palmar surface and one on the dorsal surface of the hand. The air temperature inside the mini-chamber was 0, 4, 10 and 16°C. With the contact cold exposure, the subjects touched at constant pressures an aluminium cube cooled to temperatures of –7, 0 and 7°C in the same mini-chamber. ContactT
sk was measured on the finger pad of the index finger of the left hand. TheT
sk of the proximal phalanx of the index finger (on both palm and back sides), and of the middle phalanx of the little finger was also measured. The variation ofT
sk between the proximal and the distal phalanx of the index finger was between 1.5 to 10°C during the convective cold exposure to an air temperature of 0°C. Considerable gradients persisted between the hand and fingers (from 2 to 17°C at 0°C air temperature) and between the phalanges of the finger (from 0.5 to 11.4°C at 0°C air temperature). The onset of cold induced vasodilatation (CIVD) on different fingers varied from about 5 to 15 min and it did not always appear in every finger. For contact cold exposure, whenT
sk on the contact skin cooled down to nearly 0°C, the temperature at the area close to the contact skin could still be 30°C. Some cases of CIVD were observed in the contact skin area, but not on other measuring points of the same finger. These results indicated that local thermal stimuli were the main determinents of CIVD. Representative hand skin temperature may require five or more measuring points. Our results strongly emphasised a need to consider the large spatial and individual variations in the prediction and modelling of extremity cooling. 相似文献
944.
de Astorza B Cortés G Crespí C Saus C Rojo JM Albertí S 《Infection and immunity》2004,72(3):1767-1774
The airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense. 相似文献
945.
946.
The thermal responses of neonates during a cool acclimation period were studied with regard to sleep stages. Sleep stages, body temperatures and metabolic rate (VO2) were studied for seven neonates nursed in incubators and exposed to a cool temperature (thermoneutrality minus 2 degrees C) for 75 h. Each recording session lasted 3 h in the morning: firstly under thermoneutral baseline conditions, then during the first and last 3-h periods of the cool acclimation and finally during the last 3 h of a 24-h recovery period. Sleep structure was modified during the initial hours of cool exposure: the percentage of active sleep increased (AS: +13%, P = 0.028) at the expense of quiet sleep (QS: -11%, P = 0.043). This alteration in sleep structure persisted at the end of the acclimation period. Metabolic heat production only increased in the later period of cool acclimation. Throughout the cool exposure, VO2 increased more (P = 0.040) in QS (+33%) than in AS (+20%) so that by the end of the cool period, VO2 levels were similar in both sleep stages. During cool acclimation, the maintenance of homeothermy is related not only to a change in sleep organization but also to modifications in the thermoregulatory processes in both sleep stages. Considering the importance of AS/QS patterns in the neurobehavioral development of neonates, the present results could have clinical implications for the thermal management of neonates. 相似文献
947.
E Authié D K Muteti Z R Mbawa J D Lonsdale-Eccles P Webster C W Wells 《Molecular and biochemical parasitology》1992,56(1):103-116
A 33-kDa protein of Trypanosoma congolense is a major antigen in infected cattle and the production of antibody to this antigen appeared to correlate with enhanced resistance to trypanosomiasis [4]. Immunoelectron microscopy using a monoclonal antibody (mAb 4C5) raised against the 33-kDa antigen showed a lysosomal localisation, similar to that of a previously described 32-kDa cysteine protease of T. congolense. Both mAb 4C5 and anti-33 kDa antibody from infected cattle bound on Western blots to the cysteine protease that had been purified by affinity chromatography on cystatin-Sepharose. Sepharose-coupled mAb 4C5 was used to affinity purify the antigen from bloodstream forms of T. congolense. On sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), the affinity-purified antigen had a molecular mass of 33 kDa under non-reducing conditions, and 40 kDa under reducing conditions. Anti-33-kDa antibody from infected cattle bound to both non-reduced and reduced affinity-purified antigen on Western blots. Serum from a rabbit immunised with the biochemically purified enzyme also bound the affinity-purified antigen. The affinity-purified antigen displayed proteolytic activity in fibrinogen-containing SDS-PAGE and against Azocoll. It hydrolysed benzyloxycarbonyl-Phe-Arg-7-amino-methyl coumarin (Z-Phe-Arg-NHMec) with a Km similar to that of the biochemically purified enzyme. Proteolytic and peptidolytic activities of the antigen were inhibited by the inhibitors of cysteine proteases, cystatin and trans-epoxysuccinyl-L-leucyl-amido (4-guanidino)butane (E-64). On two-dimensional gel electrophoresis, the antigen displayed similar characteristics to those of the biochemically purified enzyme. We conclude that the 33-kDa antigen of T. congolense and the cysteine protease are the same molecule. 相似文献
948.
The anatomical relationships between pro-opiomelanocortin-containing axons and serotonin neurons in the nucleus raphe dorsalis (NRD) of the rat were examined at the light microscope level with antibodies against CLIP (corticotropin-like intermediate lobe peptide), alpha-MSH (alpha-melanocyte-stimulating hormone) and serotonin. Sequential double labeling was performed with either immunofluorescence or peroxidase-antiperoxidase techniques. It was observed that the network of POMC-immunoreactive axons displayed a gradient of decreasing density from rostral to caudal levels and from dorsal to ventral parts or the NRD. The examples of close proximity between immunoreactive axons and serotonin cell bodies or dendrites were rather scarce. On the whole, the immunoreactive fibers seemed to run quasi-independently of the serotonin neurons. 相似文献
949.
Spontaneous secretion of thyroid autoantibodies by cultured peripheral blood lymphocytes from patients with Hashimoto''s thyroiditis detected by micro-ELISA techniques 下载免费PDF全文
P Benveniste B E Wenzel A Khalil V V Row R Volpé 《Clinical and experimental immunology》1984,58(2):273-282
The spontaneous in vitro production of anti-thyroglobulin (aTg) and anti-microsomal (aM) antibodies by mononuclear cells (MNC) from patients with Hashimoto's thyroiditis (HT) was analysed by an ELISA detection system. MNC from 35 HT patients spontaneously produced detectable levels of both autoantibodies in vitro (i.e., without mitogenic or antigenic stimulation). aTg was quantified using a reference aTg IgG standard and ranged from 55 to 9,000 ng aTg. Specificity of aTg by ELISA was assessed using heterologous Tg antigen (Ag). Microsomal Ag obtained by gel filtration was far less contaminated with Tg than the ultracentrifugation pellet. Specificity of aM ELISA was assessed using insulinoma membrane as unrelated Ag and by blocking aM detection only with microsomal Ag. aM levels in the 35 supernatants ranged from 0.1 to 1.12 OD. A direct correlation was found between aM serum titres detected by haemagglutination and in vitro aM spontaneous production, but not for aTg. This lack of correlation for aTg might have biological relevance. Tg restimulation in vitro enhanced aTg production in only four out of 18 cases, of which only one was significant. This system provides a tool for studies of the immunoregulation of thyroid autoantibody formation in vitro. 相似文献
950.
Teresa Sagalés Victor Gimeno M. Dolores de la Calzada Francesc Casellas M. Dolors Macià M. Villar Soriano 《Brain topography》1990,2(3):221-228
Summary Topographical analysis of cerebral electrical activity was performed in 44 patients with hepatic encephalopathy. These patients were classified in 5 groups according to clinical criteria. Eight healthy subjects were used as a control group. All were studied in an awake, eyes closed, condition and some [Control Group (CG), Group 0 (G0), Group 1 (G1) and Group 2 (G2)] also in an awake, eyes open, condition. The awake, eyes closed, maps showed marked differences in the power spectral density (PSD) of the different bands, when comparing normal subjects with patients with several degrees of hepatic encephalopathy. These differences were related to the degree of clinical involvement, mainly in the alpha and delta PSD bands. The combination of a decreased alpha PSD, increased delta PSD, and decreased mean dominant frequency (MDF) allowed a clear discrimination between the different clinical groups. The differences observed between awake, eyes closed, and awake, eyes open, conditions were especially helpful to discriminate between CG subjects and G0, G1 and G2 patients. 相似文献