全文获取类型
收费全文 | 6701篇 |
免费 | 361篇 |
国内免费 | 50篇 |
专业分类
耳鼻咽喉 | 76篇 |
儿科学 | 107篇 |
妇产科学 | 99篇 |
基础医学 | 886篇 |
口腔科学 | 534篇 |
临床医学 | 474篇 |
内科学 | 1666篇 |
皮肤病学 | 102篇 |
神经病学 | 883篇 |
特种医学 | 173篇 |
外科学 | 924篇 |
综合类 | 28篇 |
一般理论 | 4篇 |
预防医学 | 313篇 |
眼科学 | 157篇 |
药学 | 370篇 |
中国医学 | 28篇 |
肿瘤学 | 288篇 |
出版年
2024年 | 3篇 |
2023年 | 71篇 |
2022年 | 146篇 |
2021年 | 293篇 |
2020年 | 183篇 |
2019年 | 236篇 |
2018年 | 272篇 |
2017年 | 151篇 |
2016年 | 191篇 |
2015年 | 247篇 |
2014年 | 307篇 |
2013年 | 347篇 |
2012年 | 536篇 |
2011年 | 616篇 |
2010年 | 304篇 |
2009年 | 267篇 |
2008年 | 477篇 |
2007年 | 432篇 |
2006年 | 407篇 |
2005年 | 358篇 |
2004年 | 324篇 |
2003年 | 274篇 |
2002年 | 246篇 |
2001年 | 47篇 |
2000年 | 37篇 |
1999年 | 30篇 |
1998年 | 46篇 |
1997年 | 25篇 |
1996年 | 32篇 |
1995年 | 22篇 |
1994年 | 18篇 |
1993年 | 19篇 |
1992年 | 17篇 |
1991年 | 10篇 |
1990年 | 14篇 |
1989年 | 8篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 11篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1972年 | 5篇 |
1966年 | 3篇 |
排序方式: 共有7112条查询结果,搜索用时 31 毫秒
991.
Andreote FD Rossetto PB Souza LC Marcon J Maccheroni W Azevedo JL Araújo WL 《Journal of basic microbiology》2008,48(5):338-346
Harmless bacteria inhabiting inner plant tissues are termed endophytes. Population fluctuations in the endophytic bacterium Pantoea agglomerans associated with two species of field cultured citrus plants were monitored over a two-year period. The results demonstrated that populations of P. agglomerans fluctuated in Citrus reticulata but not C. sinensis. A cryptic plasmid pPA3.0 (2.9 kb) was identified in 35 out of 44 endophytic isolates of P. agglomerans and was subsequently sequenced. The origins of replication were identified and nine out of 18 open reading frames (ORFs) revealed homology with described proteins. Notably, two ORFs were related to cellular transport systems and plasmid maintenance. Plasmid pPA3.0 was cloned and the gfp gene inserted to generate the pPAGFP vector. The vector was introduced into P. agglomerans isolates and revealed stability was dependent on the isolate genotype, ninety-percent stability values were reached after 60 hours of bacterial cultivation in most evaluated isolates. In order to definitively establish P. agglomerans as an endophyte, the non-transformed bacterium was reintroduced into in vitro cultivated seedlings and the density of inner tissue colonization in inoculated plants was estimated by bacterium re-isolation, while the tissue niches preferred by the bacterium were investigated by scanning electronic microscopy (SEM). Cells from P. agglomerans (strain ARB18) at similar densities were re-isolated from roots, stems and leaves and colonization of parenchyma and xylem tissues were observed. Data suggested that P. agglomerans is a ubiquitous citrus endophyte harboring cryptic plasmids. These characteristics suggest the potential to use the bacterium as a vehicle to introduce new genes in host plants via endophytic bacterial transformation. 相似文献
992.
The Olympic brain. Does corticospinal plasticity play a role in acquisition of skills required for high-performance sports? 总被引:2,自引:1,他引:1
Non-invasive electrophysiological and imaging techniques have recently made investigation of the intact behaving human brain possible. One of the most intriguing new research areas that have developed through these new technical advances is an improved understanding of the plastic adaptive changes in neuronal circuitries underlying improved performance in relation to skill training. Expansion of the cortical representation or modulation of corticomotor excitability of specific muscles engaged in task performance is required for the acquisition of the skill. These changes at cortical level appear to be paralleled by changes in transmission in spinal neuronal circuitries, which regulate the contribution of sensory feedback mechanisms to the execution of the task. Such adaptive changes also appear to be essential for the consolidation of a memory of performance of motor tasks and thus for the lasting ability of performing highly skilled movements such as those required for Olympic sports. 相似文献
993.
Potenza L Luppi M Barozzi P Rossi G Cocchi S Codeluppi M Pecorari M Masetti M Di Benedetto F Gennari W Portolani M Gerunda GE Lazzarotto T Landini MP Schulz TF Torelli G Guaraldi G 《The New England journal of medicine》2008,359(6):593-602
Syncytial giant-cell hepatitis is a rare but severe form of hepatitis that is associated with autoimmune diseases, drug reactions, and viral infections. We used serologic, molecular, and immunohistochemical methods to search for an infectious cause in a case of syncytial giant-cell hepatitis that developed in a liver-transplant recipient who had latent infection with variant B of human herpesvirus 6 (HHV-6B) and who had received the organ from a donor with variant A latent infection (HHV-6A). At the onset of the disease, the detection of HHV-6A (but not HHV-6B) DNA in plasma, in affected liver tissue, and in single micromanipulated syncytial giant cells with the use of two different polymerase-chain-reaction (PCR) assays indicated the presence of active HHV-6A infection in the patient. Expression of the HHV-6A-specific early protein, p41/38, but not of the HHV-6B-specific late protein, p101, was demonstrated only in liver syncytial giant cells in the absence of other infectious pathogens. The same markers of HHV-6A active infection were documented in serial follow-up samples from the patient and disappeared only at the resolution of syncytial giant-cell hepatitis. Neither HHV-6B DNA nor late protein was identified in the same follow-up samples from the patient. Thus, HHV-6A may be a cause of syncytial giant-cell hepatitis. 相似文献
994.
Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events 总被引:1,自引:0,他引:1
Nardella C Chen Z Salmena L Carracedo A Alimonti A Egia A Carver B Gerald W Cordon-Cardo C Pandolfi PP 《Genes & development》2008,22(16):2172-2177
The mammalian target of rapamycin (mTOR) represents a critical signaling crossroad where pathways commonly disrupted in cancer converge. We report here that Rheb GTPase, the upstream activator of the mTOR complex 1 (mTORC1) is amplified in human prostate cancers. We demonstrate that Rheb overexpression promotes hyperplasia and a low-grade neoplastic phenotype in the mouse prostate while eliciting a concomitant senescence response and a negative feedback loop limiting Akt activation. Importantly, we show that Pten haploinsufficiency cooperates with Rheb overexpression to markedly promote prostate tumorigenesis. We conclude that Rheb acts as a proto-oncogene in the appropriate genetic milieu and signaling context. 相似文献
995.
Sacconi S Salviati L Nishigaki Y Walker WF Hernandez-Rosa E Trevisson E Delplace S Desnuelle C Shanske S Hirano M Schon EA Bonilla E De Vivo DC DiMauro S Davidson MM 《Human molecular genetics》2008,17(12):1814-1820
Mutations in mitochondrial DNA (mtDNA) tRNA genes can be considered functionally recessive because they result in a clinical or biochemical phenotype only when the percentage of mutant molecules exceeds a critical threshold value, in the range of 70-90%. We report a novel mtDNA mutation that contradicts this rule, since it caused a severe multisystem disorder and respiratory chain (RC) deficiency even at low levels of heteroplasmy. We studied a 13-year-old boy with clinical, radiological and biochemical evidence of a mitochondrial disorder. We detected a novel heteroplasmic C>T mutation at nucleotide 5545 of mtDNA, which was present at unusually low levels (<25%) in affected tissues. The pathogenic threshold for the mutation in cybrids was between 4 and 8%, implying a dominant mechanism of action. The mutation affects the central base of the anticodon triplet of tRNA(Trp) and it may alter the codon specificity of the affected tRNA. These findings introduce the concept of dominance in mitochondrial genetics and pose new diagnostic challenges, because such mutations may easily escape detection. Moreover, similar mutations arising stochastically and accumulating in a minority of mtDNA molecules during the aging process may severely impair RC function in cells. 相似文献
996.
LETM1, deleted in Wolf-Hirschhorn syndrome is required for normal mitochondrial morphology and cellular viability 总被引:2,自引:0,他引:2
Dimmer KS Navoni F Casarin A Trevisson E Endele S Winterpacht A Salviati L Scorrano L 《Human molecular genetics》2008,17(2):201-214
Wolf-Hirschhorn syndrome (WHS) is a complex congenital syndrome caused by a monoallelic deletion of the short arm of chromosome 4. Seizures in WHS have been associated with deletion of LETM1 gene. LETM1 encodes for the human homologue of yeast Mdm38p, a mitochondria-shaping protein of unclear function. Here we show that human LETM1 is located in the inner membrane, exposed to the matrix and oligomerized in higher molecular weight complexes of unknown composition. Down-regulation of LETM1 did not disrupt these complexes, but led to DRP1-independent fragmentation of the mitochondrial network. Fragmentation was not associated with changes in the levels of respiratory chain complexes, or with obvious or latent mitochondrial dysfunction, but was recovered by nigericin, which catalyzes the electroneutral exchange of K+ against H+. Down-regulation of LETM1 caused 'necrosis-like' death, without activation of caspases and not inhibited by overexpression of Bcl-2. Primary fibroblasts from a WHS patient displayed reduced LETM1 mRNA and protein, but mitochondrial morphology was surprisingly unaffected, raising the question of whether and how WHS patients counteract the consequences of monoallelic deletion of LETM1. LETM1 highlights the relationship between mitochondrial ion homeostasis, integrity of the mitochondrial network and cell viability. 相似文献
997.
Spinazzi M Cazzola S Bortolozzi M Baracca A Loro E Casarin A Solaini G Sgarbi G Casalena G Cenacchi G Malena A Frezza C Carrara F Angelini C Scorrano L Salviati L Vergani L 《Human molecular genetics》2008,17(21):3291-3302
Autosomal dominant optic atrophy (ADOA), the commonest cause of inherited optic atrophy, is caused by mutations in the ubiquitously expressed gene optic atrophy 1 (OPA1), involved in fusion and biogenesis of the inner membrane of mitochondria. Bioenergetic failure, mitochondrial network abnormalities and increased apoptosis have all been proposed as possible causal factors. However, their relative contribution to pathogenesis as well as the prominent susceptibility of the retinal ganglion cell (RGC) in this disease remains uncertain. Here we identify a novel deletion of OPA1 gene in the GTPase domain in three patients affected by ADOA. Muscle biopsy of the patients showed neurogenic atrophy and abnormal morphology and distribution of mitochondria. Confocal microscopy revealed increased mitochondrial fragmentation in fibroblasts as well as in myotubes, where mitochondria were also unevenly distributed, with clustered organelles alternating with areas where mitochondria were sparse. These abnormalities were not associated with altered bioenergetics or increased susceptibility to pro-apoptotic stimuli. Therefore, changes in mitochondrial shape and distribution can be independent of other reported effects of OPA1 mutations, and therefore may be the primary cause of the disease. The arrangement of mitochondria in RGCs, which degenerate in ADOA, may be exquisitely sensitive to disturbance, and this may lead to bioenergetic crisis and/or induction of apoptosis. Our results highlight the importance of mitochondrial dynamics in the disease per se, and point to the loss of the fine positioning of mitochondria in the axons of RGCs as a possible explanation for their predominant degeneration in ADOA. 相似文献
998.
Mattarucchi E Guerini V Rambaldi A Campiotti L Venco A Pasquali F Lo Curto F Porta G 《Genes, chromosomes & cancer》2008,47(7):625-632
Reciprocal translocation t(9;22) is central to the pathogenesis of chronic myeloid leukemia. Some authors have suggested that Alu repeats facilitate this process, but supporting analyses have been sparse and often anecdotal. The purpose of this study was to analyze the local structure of t(9;22) translocations and assess the relevance of interspersed repeat elements at breakpoints. Collected data have been further compared with the current models of DNA recombination, in particular the single-strand annealing (SSA) and the nonhomologous end joining (NHEJ) processes. We developed a protocol for the rapid characterization of patient-specific genomic junctions and analyzed 27 patients diagnosed with chronic myeloid leukemia. Sequence analysis revealed microhomologies at the junctions of 21 patients of 27, while interspersed repeats were of relevance (P < 0.05) in at least 16 patients. These findings are more frequent than expected and give an indication that the main mechanisms involved in the t(9;22) translocation are the SSA and NHEJ pathways, both playing a role. Furthermore, our report is consistent with microhomologies facilitating the joining of DNA ends in the translocation process, and with both Alu and a variety of other repeat sequences pairing nonhomologous chromosomes during the SSA pathway. 相似文献
999.
Pitch differences between concurrent sounds are important cues used in auditory scene analysis and also play a major role in music perception. To investigate the neural codes underlying these perceptual abilities, we recorded from single fibers in the cat auditory nerve in response to two concurrent harmonic complex tones with missing fundamentals and equal-amplitude harmonics. We investigated the efficacy of rate-place and interspike-interval codes to represent both pitches of the two tones, which had fundamental frequency (F0) ratios of 15/14 or 11/9. We relied on the principle of scaling invariance in cochlear mechanics to infer the spatiotemporal response patterns to a given stimulus from a series of measurements made in a single fiber as a function of F0. Templates created by a peripheral auditory model were used to estimate the F0s of double complex tones from the inferred distribution of firing rate along the tonotopic axis. This rate-place representation was accurate for F0s greater, similar900 Hz. Surprisingly, rate-based F0 estimates were accurate even when the two-tone mixture contained no resolved harmonics, so long as some harmonics were resolved prior to mixing. We also extended methods used previously for single complex tones to estimate the F0s of concurrent complex tones from interspike-interval distributions pooled over the tonotopic axis. The interval-based representation was accurate for F0s less, similar900 Hz, where the two-tone mixture contained no resolved harmonics. Together, the rate-place and interval-based representations allow accurate pitch perception for concurrent sounds over the entire range of human voice and cat vocalizations. 相似文献
1000.