全文获取类型
收费全文 | 443000篇 |
免费 | 13532篇 |
国内免费 | 1903篇 |
专业分类
耳鼻咽喉 | 4940篇 |
儿科学 | 11881篇 |
妇产科学 | 10848篇 |
基础医学 | 56477篇 |
口腔科学 | 7830篇 |
临床医学 | 41122篇 |
内科学 | 92407篇 |
皮肤病学 | 8890篇 |
神经病学 | 38648篇 |
特种医学 | 14248篇 |
外国民族医学 | 89篇 |
外科学 | 56066篇 |
综合类 | 9971篇 |
现状与发展 | 3篇 |
一般理论 | 369篇 |
预防医学 | 35951篇 |
眼科学 | 9083篇 |
药学 | 29058篇 |
6篇 | |
中国医学 | 1863篇 |
肿瘤学 | 28685篇 |
出版年
2023年 | 168篇 |
2022年 | 195篇 |
2021年 | 200篇 |
2020年 | 191篇 |
2019年 | 283篇 |
2018年 | 363篇 |
2016年 | 167篇 |
2015年 | 233篇 |
2014年 | 492篇 |
2013年 | 312篇 |
2012年 | 45924篇 |
2011年 | 49095篇 |
2010年 | 7575篇 |
2009年 | 5059篇 |
2008年 | 39993篇 |
2007年 | 41991篇 |
2006年 | 41650篇 |
2005年 | 40567篇 |
2004年 | 35735篇 |
2003年 | 34025篇 |
2002年 | 30260篇 |
2001年 | 21907篇 |
2000年 | 29046篇 |
1999年 | 12596篇 |
1998年 | 1995篇 |
1997年 | 1024篇 |
1996年 | 814篇 |
1995年 | 740篇 |
1994年 | 680篇 |
1993年 | 609篇 |
1992年 | 498篇 |
1991年 | 466篇 |
1990年 | 412篇 |
1989年 | 166篇 |
1988年 | 160篇 |
1987年 | 145篇 |
1986年 | 147篇 |
1985年 | 190篇 |
1984年 | 236篇 |
1983年 | 197篇 |
1982年 | 188篇 |
1981年 | 154篇 |
1959年 | 787篇 |
1958年 | 1681篇 |
1957年 | 1841篇 |
1956年 | 1631篇 |
1955年 | 1653篇 |
1954年 | 1565篇 |
1949年 | 266篇 |
1948年 | 307篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Machlitt A Kuepferling P Bommer C Koerner H Chaoui R 《American journal of medical genetics. Part A》2005,(2):207-211
We report on a midtrimester fetus with multiple malformations, who was prenatally found to have pure partial trisomy 1q with duplication 1q21-qter. Prenatal ultrasound at 23 gestational weeks demonstrated craniofacial dysmorphism, ventriculomegaly, hand anomalies, and multiple visceral anomalies including cardiac defect, duodenal atresia, omphalocele, and urethral obstruction in the fetus. After pregnancy termination, external morphologic examination confirmed the sonographic characteristics, but autopsy was refused. Cytogenetic analysis (GTG banding) and subtelomeric probes (FISH) demonstrated an aberrant karyotype 46,XY,der(1)(1qter --> 1q21::1p36.3 --> 1qter) in a total of 139 amniotic fluid cells. Trisomy of the long arm of chromosome 1 is a rare condition. Large duplications of almost the entire 1q had so far been described in five mosaic cases. The present case and review of the literature suggest that duplication 1q21-qter is a serious condition with pre- or perinatal demise of all reported cases. This case further delineates the phenotype in trisomy 1q. 相似文献
992.
Bb2Bb3 regulation of murine Lyme arthritis is distinct from Ncf1 and independent of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase 下载免费PDF全文
Crandall H Ma Y Dunn DM Sundsbak RS Zachary JF Olofsson P Holmdahl R Weis JH Weiss RB Teuscher C Weis JJ 《The American journal of pathology》2005,167(3):775-785
Several quantitative trait loci regulating murine Lyme arthritis severity have been mapped, including a highly significant linkage found on chromosome 5, termed Bb2Bb3. Within this region, the Ncf1 gene of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has recently been identified as a major regulator of arthritis severity in rodent models of rheumatoid arthritis, an effect attributed to protective properties of reactive oxygen species. To assess the role of Ncf1 in Lyme arthritis, we introgressed Bb2Bb3 from severely arthritic C3H/He mice onto mildly arthritic C57BL/6 mice. This increased Lyme arthritis severity, whereas the reciprocal transfer conferred protection from disease. A single nucleotide polymorphism was identified in the Ncf1 gene that did not influence the protein sequence or expression of Ncf1. Although polymorphonuclear leukocytes from C57BL/6 mice generated a greater oxidative burst than polymorphonuclear leukocytes from C3H/He mice, studies with the Bb2Bb3 congenic mice demonstrated this difference was not linked to Ncf1 alleles. Furthermore, Lyme arthritis severity was not altered in mice lacking either the Ncf1 or Gp91phox subunits of the NADPH oxidase complex. Together, these results argue that Ncf1 is not a candidate gene for regulation of Lyme arthritis and reveal Lyme arthritis to be independent of NADPH oxidase activity, distinguishing it from other models of rheumatoid arthritis. 相似文献
993.
Multilocus sequence typing of methicillin-resistant Staphylococcus aureus from an area of low endemicity by real-time PCR 下载免费PDF全文
A protocol for multilocus sequence typing (MLST) of methicillin-resistant Staphylococcus aureus (MRSA) was adapted to real-time LightCycler System PCR for efficient and rapid amplification of seven housekeeping genes in the same PCR run and real-time detection of the products. The method was evaluated on a representative and well-characterized collection of clinical MRSA isolates (n = 57) obtained from an area of low endemicity. Twenty sequence types (STs) and nine clonal complexes were identified. Combining STs and the staphylococcal cassette chromosome mec (SCCmec) type identified 27 different genotypes, and type IV SCCmec was present in 11 different STs. The presence of the Panton Valentine leukocidin (PVL) genes was found in isolates of four different STs. Eleven different STs were found among the community-acquired as well as among the hospital-acquired MRSA. The genetic heterogeneity was also denoted by pulsed-field gel electrophoresis analysis that showed 24 different pulsotypes among the 57 MRSA isolates. The presence of more than one different type of SCCmec in the same ST indicates that the MRSA clones have arisen at several occasions in the same genetic background by independent acquisition of SCCmec into methicillin-sensitive strains. This circumstance shows the importance of combining MLST data with SCCmec-typing results when investigating the origins of MRSA. 相似文献
994.
Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons 总被引:3,自引:0,他引:3
Lundström A Gallio M Englund C Steneberg P Hemphälä J Aspenström P Keleman K Falileeva L Dickson BJ Samakovlis C 《Genes & development》2004,18(17):2161-2171
Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse. 相似文献
995.
Ribosomal RNA of Nosema algerae and phylogenetic relationship to other microsporidia 总被引:1,自引:0,他引:1
Microsporidia are intracellular parasites that are common in invertebrates. Taxonomic classification is mostly restricted
to morphologic and physiologic data. Limited data are available about taxonomic classification using DNA-sequence data for
analysis. We examined the small-subunit (SSU) rDNA, the intergenic spacer (ITS) region, and a part of the large-subunit (LSU)
rDNA of Nosema algerae, a parasite of mosquitoes, taken from a laboratory colony of Anopheles stephensi. Target gene amplifications were done by polymerase chain reaction (PCR) and, after cloning, DNA fragments were sequenced.
The SSU-rDNA sequence obtained was aligned with several other microsporidian SSU-rDNA sequences available from the GenBank
or EMBL data bases and was analyzed by different methods. On the basis of the results of our phylogenetic analysis, we suggest
that our N. algerae isolate is not closely related to other microsporidia belonging to the genus Nosema.
Received: 31 May 1999 / Accepted: 27 July 1999 相似文献
996.
Neuronal programmed cell death is regulated by a neurotrophic supply from targets and afferent inputs. The relative contribution of each component varies according to neuronal type and age. We have previously reported that primary cultures of cerebellar granule cells undergo apoptosis when deprived of depolarising KCl concentrations, suggesting a significant role of afferent inputs in the control of cerebellar granule cells survival. This issue was investigated by setting up various in vivo lesional paradigms in order to obtain partial or total deafferentation of the cerebellar granule layer in adult rats. At different times after surgery, cerebellar sections were subjected to TUNEL staining in order to detect possible DNA damage. One week after unilateral pedunculotomy, few scattered groups of apoptotic granule neurons were observed in the homolateral hemisphere. On the contrary, total deafferentation obtained by a new experimental paradigm based on an "L-cut" lesion induced massive and widespread apoptotic death in the granule layer of the deafferentated area. The time window of DNA fragmentation in granule layer was one to seven days after the "L-cut". Selective Purkinje cell deafferentation obtained by 3-acetylpyridine injection did not result in TUNEL staining in the cerebellar cortex. The current finding that mossy fiber axotomy induces granule cell apoptotic death points out for the first time the crucial role of afferent inputs in mature granule cell survival. Moreover, the in vivo lesional model described here may prove to be an useful tool for investigating cellular and molecular mechanisms of neuronal death triggered by deafferentation. 相似文献
997.
Cytokeratin 8 protects from hepatotoxicity, and its ratio to cytokeratin 18 determines the ability of hepatocytes to form Mallory bodies 总被引:10,自引:0,他引:10 下载免费PDF全文
Zatloukal K Stumptner C Lehner M Denk H Baribault H Eshkind LG Franke WW 《The American journal of pathology》2000,156(4):1263-1274
In alcoholic hepatitis, a severe form of alcohol-induced toxic liver injury, as well as in experimental intoxication of mice with the porphyrinogenic drugs griseofulvin and 3,5-diethoxycarbonyl-1, 4-dihydrocollidine, hepatocytes form cytoplasmic protein aggregates (Mallory bodies; MBs) containing cytokeratins (CKs) and non-CK components. Here we report that mice lacking the CK8 gene and hence CK intermediate filaments in hepatocytes, but still expressing the type I partner, ie, the CK18 gene, do not form MBs but suffer from extensive porphyria and progressive toxic liver damage, leading to the death of a considerable number of animals (7 of 12 during 12 weeks of intoxication). Our observations show that 1) in the absence of CK8 as well as in the situation of a relative excess of CK18 over CK8 no MBs are formed; 2) the loss of CK8 is not compensated by other type II CKs; and 3) porphyria and toxic liver damage are drastically enhanced in the absence of CK8. Our results point to a protective role of CKs in certain types of toxic liver injury and suggest that MBs by themselves are not harmful to hepatocytes but may be considered as a product of a novel defense mechanism in hepatocytes. 相似文献
998.
In temporal lobe epilepsy, the occurrence of seizures seems to correlate with the presence of lesions underlying the establishment of a hyperexcitable circuit. However, in the lithium-pilocarpine model of epilepsy, neuronal damage occurs both in the structures belonging to the circuit of initiation and maintenance of the seizures (forebrain limbic system) as in the propagation areas (cortex and thalamus) and in the circuit of remote control of seizures (substantia nigra pars reticulata). To determine whether or not we could protect the brain from lesions and epileptogenesis induced by status epilepticus and identify cerebral structures involved in the genesis of epilepsy, we studied the effects of the chronic exposure to non-deleterious seizures, either focalized with secondary generalization (amygdala kindling, kindled-pilocarpine rats), or primary generalized (ear-clip electroshocks, electroshock-pilocarpine rats) on neuronal damage and epileptogenesis induced by lithium-pilocarpine status epilepticus. These animals were compared to rats subjected to status epilepticus but not pretreated with seizures (sham-kindled-pilocarpine or sham-electroshock-pilocarpine rats). Compared to sham-pilocarpine rats, neuronal damage was prevented in the limbic system of the kindled-pilocarpine rats, except in the hilus of the dentate gyrus and the entorhinal cortex, while it was enhanced in rats pretreated with electroshocks, mainly in the entorhinal and perirhinal cortices. Most sham-kindled- and sham-electroshock-pilocarpine rats (92-100%) developed recurrent seizures after a silent period of 40-54days. Likewise, all kindled-pilocarpine rats developed spontaneous seizures after the same latency as their sham controls, while only two of 10 electroshock-pilocarpine rats became epileptic after a delay of 106-151days.The present data show that the apparent antiepileptic properties of electroshocks correlate with extensive damage in midbrain cortical regions, which may prevent the propagation of seizures from the hippocampus and inhibit their motor expression. Conversely, the extensive neuroprotection of the limbic system but not the hilus and entorhinal cortex provided by amygdala kindling does not prevent epileptogenesis. Thus, the hilus, the entorhinal and/or perirhinal cortex may be key structure(s) for the establishment of epilepsy. 相似文献
999.
Murray HW Jungbluth A Ritter E Montelibano C Marino MW 《Infection and immunity》2000,68(11):6289-6293
Tumor necrosis factor (TNF)-deficient mice were challenged with Leishmania donovani to characterize TNF in the response of visceral intracellular infection to antileishmanial chemotherapy. In wild-type controls (i) liver infection peaked at week 2 and resolved, (ii) discrete liver granulomas developed at weeks 2 to 4 and involuted, and (iii) leishmanicidal responses to antimony (Sb), amphotericin B (AmB), and miltefosine were intact. In TNF knockout (KO) mice (i) initial liver infection was unrestrained, plateaued, and then declined somewhat by week 6, (ii) an absent early granulomatous reaction abruptly accelerated with striking tissue inflammation, widespread hepatic necrosis, and 100% mortality by week 10, and (iii) while the initial response to AmB and miltefosine was intact, killing induced by Sb therapy was reduced by >50%. Although initial AmB treatment during weeks 2 to 3 killed 98% of liver parasites, 75% of AmB-treated KO mice subsequently relapsed and died by week 12; however, additional maintenance AmB preserved long-term survival. These results for a model of visceral infection indicate that endogenous TNF is required early on to control intracellular L. donovani, support granuloma development, and mediate optimal initial effects of Sb and prevent relapse after ordinarily curative AmB treatment. A compensatory, TNF-independent antileishmanial mechanism developed in TNF KO mice; however, its effect was uncontrolled fatal inflammation. Chemotherapeutic elimination of the parasite stimulus reversed the hyperinflammatory response and preserved survival. 相似文献
1000.
Berthier R Martinon-Ego C Laharie AM Marche PN 《Journal of immunological methods》2000,239(1-2):95-107
Dendritic cells (DC) are professional antigen presenting cells (APC) able to activate naive T cells and initiate the immune response. They are present in most tissues at very low concentrations and are difficult to isolate. DC can be obtained in larger numbers by their propagation from progenitors present in blood, bone marrow and spleen. However, biochemical studies and biological analysis of DC functions require very large numbers of these cells. In this paper, we described a two-step culture system using unfractionated splenocytes from BALB/c mice as a source of DC progenitors. The proliferative capacity of the progenitors is amplified in the first step of the culture (day 0-6) using different combinations of early acting cytokines combined or not with granulocyte-macrophage CSF (GM-CSF). The second step of the culture starts at day 6 with the removal of early growth factors in order to allow the differentiation and final maturation of DC during 2-3 weeks of culture with flt-3 ligand (flt-3L) and GM-CSF. The addition of Stem Cell Factor (SCF) or IL-6 to the standard combination of flt-3L+/-GM-CSF produces a large increase in the proliferation of GM and DC progenitors (28 times and 11 times respectively) in the first step of the culture. This proliferative wave of DC progenitors is followed by the production of a high percentage of immature and mature DC in flt-3L+GM-CSF stimulated cultures. The best combination of early cytokines in terms of proliferative activity and subsequent level of DC production was flt-3L+IL-6+GM-CSF, which permitted the generation of 1 to 2x10(9) DC from one single spleen. Using this growth factor cocktail, a mixture of immature (2/3) and mature (1/3) DC was produced until day 14 of culture, and levels of MHC class II and costimulatory molecules (CD40, B7.2) increased between 2 and 4 weeks of incubation, or within 2 days when stimulated by IL-4 or LPS. The splenic DC produced after 2 weeks of culture are fully functional, exhibiting a high capacity of endocytosis when immature, a strong stimulatory reactivity in mixed leukocyte reaction and consistently producing high levels of bioactive IL-12 p70 after CD 40 ligation in the presence of LPS between 13 and 43 days of culture. 相似文献