全文获取类型
收费全文 | 33143篇 |
免费 | 1921篇 |
国内免费 | 158篇 |
专业分类
耳鼻咽喉 | 326篇 |
儿科学 | 803篇 |
妇产科学 | 822篇 |
基础医学 | 4864篇 |
口腔科学 | 1909篇 |
临床医学 | 2799篇 |
内科学 | 7405篇 |
皮肤病学 | 1007篇 |
神经病学 | 2875篇 |
特种医学 | 616篇 |
外科学 | 2669篇 |
综合类 | 134篇 |
一般理论 | 21篇 |
预防医学 | 3735篇 |
眼科学 | 534篇 |
药学 | 2617篇 |
中国医学 | 198篇 |
肿瘤学 | 1888篇 |
出版年
2024年 | 42篇 |
2023年 | 392篇 |
2022年 | 897篇 |
2021年 | 1580篇 |
2020年 | 900篇 |
2019年 | 1282篇 |
2018年 | 1576篇 |
2017年 | 1039篇 |
2016年 | 984篇 |
2015年 | 1240篇 |
2014年 | 1609篇 |
2013年 | 1983篇 |
2012年 | 3041篇 |
2011年 | 3216篇 |
2010年 | 1590篇 |
2009年 | 1331篇 |
2008年 | 2202篇 |
2007年 | 2118篇 |
2006年 | 1846篇 |
2005年 | 1613篇 |
2004年 | 1397篇 |
2003年 | 1169篇 |
2002年 | 1021篇 |
2001年 | 125篇 |
2000年 | 77篇 |
1999年 | 102篇 |
1998年 | 134篇 |
1997年 | 132篇 |
1996年 | 83篇 |
1995年 | 67篇 |
1994年 | 69篇 |
1993年 | 50篇 |
1992年 | 47篇 |
1991年 | 34篇 |
1990年 | 26篇 |
1989年 | 25篇 |
1988年 | 20篇 |
1987年 | 14篇 |
1986年 | 15篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 13篇 |
1982年 | 16篇 |
1981年 | 11篇 |
1980年 | 13篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1972年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Ana Velasco Victor Palomar-Asenjo Laura Ga?an Lluis Catasus Nuria Llecha Angel Panizo Victor Palomar-Garcia Miquel Quer Xavier Matias-Guiu 《Diagnostic molecular pathology》2005,14(2):109-114
The familial paraganglioma syndrome is an autosomal dominant disorder characterized by the presence of carotid body paragangliomas and, less frequently, paragangliomas of the glomus jugulare, glomus vagale, and adrenal pheochromocytomas. Germline mutations of the genes for succinate dehydrogenase subunits D, B, or C (SDHD, SDHB, SDHC) have been identified in some kindreds with familial paraganglioma. In this study, we report the clinicopathologic features of four different kindreds with familial paraganglioma, which were screened for germline mutations in the SDHD gene. DNA was obtained from tumor and normal tissue, as well as from peripheral blood. Mutation analysis was performed by single-strand conformation polymorphism analysis and DNA sequencing. SDHD germline mutations were detected in the affected family members of the four families, as well as in several asymptomatic carriers. An identical mutation in exon 4 of SDHD (334-337delACTG) was identified in two apparently unrelated kindreds. The third family showed a germline mutation in exon 2 (W43X). The mutations present in these three families had been previously described in Spanish families, suggesting a founder effect. The fourth family exhibited a mutation in exon 2 of SDHD (170-171delTT), which had not been previously identified. The affected family members of the four kindreds showed paragangliomas, located in the head and neck region, and all of them were benign. These results confirm that genetic testing of SDHD may be a powerful tool for the identification of the syndrome in patients with multiple or bilateral paragangliomas. 相似文献
102.
CD44 Isoform Expression Follows Two Alternative Splicing Pathways in Breast Tissue 总被引:1,自引:0,他引:1 下载免费PDF全文
Xavier Roca Jos L. Mate Aurelio Ariza Ana M. Muoz-Mrmol Claudia von Uexküll-Güldeband Inmaculada Pellicer Jos J. Navas-Palacios Marcos Isamat 《The American journal of pathology》1998,153(1):183-190
The repertoire of distinct CD44 protein isoforms is generated by means of alternative pre-mRNA splicing of 10 variable exons located in the central region of the CD44 gene. We have used human breast ductal carcinoma as a model to identify two alternative splicing pathways of the CD44 pre-mRNA variable region that account for the generation of all of the CD44 isoforms described in breast tissue. An alternative splicing pathway that reflects inclusion of variable exons in a gradual 3′-to-5′ fashion is evidenced in breast ductal carcinoma and its lymph node metastases. This pathway is compatible with a mechanism that generates the standard form of CD44 (devoid of variable exons) and is distinguishable from an alternative splicing pathway that involves exclusively variant exon 3 and is observable in both normal and carcinoma breast tissue. We show that both pathways are detectable in the same cell type in the breast and provide a speculative model by which these splicing routes could take place. 相似文献
103.
Jos Angel Gonzalo Ana Gonzlez-García Terje Kalland Gunnar Hedlund Carlos Martínez-A Guido Kroemer 《European journal of immunology》1993,23(9):2372-2374
Intravenous injections of 50 μ.g Staphylococcus aureus enterotoxin B (SEB) or bacterial lipopolysaccharide (LPS) are lethal, provided that mice are simultaneously sensitized with either N-galactosamine (GalN) or the anti-glucocorticoid RU-38486. Similar to the synthetic glucocorticoid (GC) receptor agonist dexamethasone, pharmacological doses of the immunomodulator linomide (quinoline-3-carboxamide) prevent death in all four models of lethal septic shock (LPS + GalN, LPS + RU-38486, SEB + GalN, and SEB + RU-38486) and inhibit the secretion of tumor necrosis factor, one of the major intermediate effector molecules of SEB and LPS toxicity. In this system, cyclosporine A (CsA), although effective in suppressing SEB toxicity, fails to counteract the lethal effect of LPS. This observation, together with the fact that linomide acts in the presence of excess amounts of GC receptor antagonist, indicates that linomide functions in a different way to that of known immunosuppressive agents like CsA and GC. 相似文献
104.
105.
Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration 下载免费PDF全文
Rozenfeld C Martinez R Figueiredo RT Bozza MT Lima FR Pires AL Silva PM Bonomo A Lannes-Vieira J De Souza W Moura-Neto V 《Infection and immunity》2003,71(4):2047-2057
The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-gamma) in the central nervous system (CNS). However, IFN-gamma-activated microglia are paradoxically involved in parasitism control and in tissue damage during a broad range of CNS pathologies. In this way, nitric oxide (NO), the main toxic metabolite produced by IFN-gamma-activated microglia, may cause neuronal injury during T. gondii infection. Despite the potential NO toxicity, neurodegeneration is not a common finding during chronic T. gondii infection. In this work, we describe a significant down-modulation of NO production by IFN-gamma-activated microglia in the presence of conditioned medium of T. gondii-infected astrocytes (CMi). The inhibition of NO production was paralleled with recovery of neurite outgrowth when neurons were cocultured with IFN-gamma-activated microglia in the presence of CMi. Moreover, the modulation of NO secretion and the neuroprotective effect were shown to be dependent on prostaglandin E(2) (PGE(2)) production by T. gondii-infected astrocytes and autocrine secretion of interleukin-10 (IL-10) by microglia. These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor. Further, the modulatory effects of CMi were mimicked by the presence of exogenous PGE(2) and by forskolin, an adenylate cyclase activator. Altogether, these data point to a T. gondii-triggered regulatory mechanism involving PGE(2) secretion by astrocytes and cAMP-dependent IL-10 secretion by microglia. This may reduce host tissue inflammation, thus avoiding neuron damage during an established Th1 protective immune response. 相似文献
106.
Campos B Díez O Odefrey F Domènech M Moncoutier V Martínez-Ferrandis JI Osorio A Balmaña J Barroso A Armengod ME Benítez J Alonso C Stoppa-Lyonnet D Goldgar D Baiget M 《Human mutation》2003,21(4):452-452
A frame-shift 9254del5 mutation was independently identified in 12 families, eleven of them with Spanish ancestors, in a BRCA2 screening performed in 841 breast and/or ovarian cancer families and in 339 women with breast cancer diagnosed before the age of 40 at different centers in France and Spain. We sought to analyze in detail the haplotype and founder effects of the 9254del5 and to estimate the time of origin of the mutation. Eight polymorphic microsatellite markers and two BRCA2 polymorphisms were used for the haplotype analyses. The markers were located flanking the BRCA2 gene spanning a region of 6.1 cM. Our results suggest that these families shared a common ancestry with BRCA2 9254del5, which is a founder mutation originating in the Northeast Spanish, with an estimated age of 92 (95% CI 56-141) generations. 相似文献
107.
Andrade MM Tomé MF Santiago ES Lúcia-Santos A de Andrade TG 《Physiology & behavior》2003,78(1):125-133
We conducted a longitudinal study about daily variation of Wistar male rats' behavior in the elevated plus-maze (EPM) evaluated in the 1st, 2nd, 3rd, 6th, 12th, and 18th months of life. Animals were submitted to the plus-maze in 12 sessions at 2-h intervals (n=72, 6 per time point). Spontaneous rest-activity rhythm of four animals was assessed by observation of 24-h videotape records. Time series were analyzed by Cosinor method. Behavioral rates on the six occasions and in light and dark phases were compared by means of two-way ANOVA with repeated measures. Exploratory behavior in EPM was smaller in the light phase and in older animals. Higher values of open and closed arms exploration were observed in the first and third months of the dark phase, and in the first month of the light phase. Adjustment to the 24-h period was significant at all stages for rest-activity data, number of entries in closed arms, and time on center, and for three to five stages for open-arm exploration. In general, 24 h variability was more pronounced in younger animals compared with older ones. The present study showed that: (1). a significant amount of total variability of the behavioral indexes analyzed could be attributed to 24 h variation, (2). light/dark phases differences in EPM exploration were present at all developmental stages, (3). older Wistar rats explored less the EPM and were less active in their home cage compared with younger ones, and (4). behavioral indexes (EPM) decrease was phase related and partially related to a reorganization of rest-activity rhythm. 相似文献
108.
Pinheiro PS Rodrigues RJ Silva AP Cunha RA Oliveira CR Malva JO 《Neuroscience letters》2003,336(2):97-100
Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been identified mostly as postsynaptic receptors mediating fast glutamatergic synaptic transmission. However, neurochemical studies based on the modulation of neurotransmitter release have suggested the existence of presynaptic AMPA receptors. We have used a recently described technique that allows a high-purity fractionation of the pre- and postsynaptic proteins of synaptic junctions to evaluate the distribution of the different AMPA receptor subunits in rat hippocampal synapses. Surprisingly, we found very high levels of GluR1- and GluR2/3-like immunoreactivity in the presynaptic fraction, but also in the postsynaptic and extrasynaptic fractions. GluR4-like immunoreactivity was much less abundant but was still detected, predominantly in the postsynaptic fraction. This methodology appears to be far more sensitive than the classical immunogold electron microscopy to determine the localization of synaptic receptors. 相似文献
109.
CD40 is required for the optimal induction of protective immunity to Mycobacterium avium 总被引:1,自引:0,他引:1 下载免费PDF全文
C57Bl/6 mice and mice deficient in the CD40 molecule were infected with three strains of Mycobacterium avium. Two of the M. avium strains proliferated more extensively in CD40-deficient (CD40-/-) mice than in control mice. The increased susceptibility to infection of CD40-/- mice was associated with the generation of poorer interleukin-12 (IL-12) p40 and interferon-gamma (IFN-gamma) responses as compared to the controls, suggesting a role for CD40 in the development of protective immunity. In contrast, direct triggering of CD40 on infected macrophages failed to induce any anti-mycobacterial activity in infected macrophages. 相似文献
110.
E-test method for testing susceptibilities of Aspergillus spp. to the new triazoles voriconazole and posaconazole and to established antifungal agents: comparison with NCCLS broth microdilution method 下载免费PDF全文
NCCLS document M38-P describes standard parameters for testing the fungistatic activities (MICs) of established agents against filamentous fungi (molds). This study evaluated the in vitro susceptibilities of 15 Aspergillus flavus isolates, 62 A. fumigatus isolates, and 10 isolates each of A. niger, A. nidulans, and A. terreus to voriconazole, posaconazole, itraconazole, and amphotericin B by the E-test and NCCLS M38-P microdilution methods. The agreement (within 3 dilutions) between methods for voriconazole was independent of the E-test incubation time (93.3 to 100% for four of five species at both incubation times). In contrast, with amphotericin B, itraconazole, and posaconazole, E-test results were more dependent on the incubation time for certain species. For A. fumigatus, posaconazole E-test MICs had better concordance with reference values after 48 h (95.2%) than after 24 h (90%), while the highest agreement for itraconazole MICs was after 24 h (90.3 versus 74.2%) of incubation. Better agreement between the methods was also obtained with 24-h E-test amphotericin B MICs for A. flavus (73.3 versus 26.7%) and A. fumigatus (96.7 versus 64.5%). E-test MICs of the four agents had the lowest percentages of agreement with reference values for A. nidulans (60 to 80%). For isolates for which high MICs were obtained for the four agents by the reference method, high MICs were also obtained by E-test at both 24 and 48 h. The utility of in vitro results of either the E-test or the NCCLS broth microdilution (M38-P) method for Aspergillus spp. needs to be established in clinical trials. 相似文献