全文获取类型
收费全文 | 27941篇 |
免费 | 2083篇 |
国内免费 | 87篇 |
专业分类
耳鼻咽喉 | 352篇 |
儿科学 | 806篇 |
妇产科学 | 546篇 |
基础医学 | 3652篇 |
口腔科学 | 395篇 |
临床医学 | 2681篇 |
内科学 | 6080篇 |
皮肤病学 | 431篇 |
神经病学 | 2642篇 |
特种医学 | 1188篇 |
外科学 | 4928篇 |
综合类 | 275篇 |
现状与发展 | 1篇 |
一般理论 | 51篇 |
预防医学 | 2046篇 |
眼科学 | 416篇 |
药学 | 1374篇 |
中国医学 | 37篇 |
肿瘤学 | 2210篇 |
出版年
2023年 | 324篇 |
2022年 | 563篇 |
2021年 | 1306篇 |
2020年 | 697篇 |
2019年 | 1017篇 |
2018年 | 1210篇 |
2017年 | 838篇 |
2016年 | 811篇 |
2015年 | 985篇 |
2014年 | 1336篇 |
2013年 | 1615篇 |
2012年 | 2384篇 |
2011年 | 2312篇 |
2010年 | 1271篇 |
2009年 | 993篇 |
2008年 | 1557篇 |
2007年 | 1610篇 |
2006年 | 1406篇 |
2005年 | 1289篇 |
2004年 | 1086篇 |
2003年 | 931篇 |
2002年 | 792篇 |
2001年 | 215篇 |
2000年 | 171篇 |
1999年 | 187篇 |
1998年 | 159篇 |
1997年 | 139篇 |
1996年 | 145篇 |
1995年 | 122篇 |
1994年 | 88篇 |
1993年 | 89篇 |
1992年 | 123篇 |
1991年 | 128篇 |
1990年 | 127篇 |
1989年 | 131篇 |
1988年 | 107篇 |
1987年 | 109篇 |
1986年 | 97篇 |
1985年 | 102篇 |
1984年 | 105篇 |
1983年 | 87篇 |
1982年 | 97篇 |
1981年 | 85篇 |
1980年 | 66篇 |
1979年 | 90篇 |
1978年 | 93篇 |
1977年 | 50篇 |
1976年 | 45篇 |
1974年 | 47篇 |
1973年 | 46篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
We studied the patterns of linkage disequilibrium (LD) in the human genome among three populations: African Americans, Caucasians and Ashkenazi Jews. These three populations represent admixed, outbred and isolated populations, respectively. The study examined defined chromosomal regions across the whole genome. We found that SNP allele frequencies are highly correlated between Ashkenazi Jews and Caucasians and somewhat distinct in African Americans. In addition, Ashkenazi Jews have a modest increase in LD compared with Caucasians, and both have greater LD than African Americans. The three populations differed more significantly with regard to haplotype heterogeneity. We found, as expected, that Ashkenazi Jews display the greatest extent of homogeneity and African Americans the greatest extent of heterogeneity. We found that most of the variance in LD can be attributed to the difference between regions and markers rather than to that between different population types. The average recombination rates estimated by low-resolution genetic maps can only explain a small fraction of the variance between regions. We found that LD (in terms of r(2)) decreases as a function of distance even within the so-called 'haplotype blocks'. This has significant consequences when using LD mapping for the genetic dissection of complex traits, as higher density SNP maps will be required to scan the genome. 相似文献
102.
Paul Kruszka Tommy Hu Sungkook Hong Rebecca Signer Benjamin Cogné Betrand Isidor Sarah E. Mazzola Jacques C. Giltay Koen L. I. van Gassen Eleina M. England Lynn Pais Charlotte W. Ockeloen Pedro A. Sanchez‐Lara Esther Kinning Darius J. Adams Kayla Treat Wilfredo Torres‐Martinez Maria F. Bedeschi Maria Iascone Stephanie Blaney Oliver Bell Tiong Y. Tan Marie‐Ange Delrue Julie Jurgens Brenda J. Barry Elizabeth C. Engle Sarah K. Savage Nicole Fleischer Julian A. Martinez‐Agosto Kym Boycott Elaine H. Zackai Maximilian Muenke 《American journal of medical genetics. Part A》2019,179(10):2075-2082
Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features. 相似文献
103.
Requirement for tumor necrosis factor receptor 2 expression on vascular cells to induce experimental cerebral malaria 下载免费PDF全文
Stoelcker B Hehlgans T Weigl K Bluethmann H Grau GE Männel DN 《Infection and immunity》2002,70(10):5857-5859
Using tumor necrosis factor receptor type 2 (TNFR2)-deficient mice and generating bone marrow chimeras which express TNFR2 on either hematopoietic or nonhematopoietic cells, we demonstrated the requirement for TNFR2 expression on tissue cells to induce lethal cerebral malaria. Thus, TNFR2 on the brain vasculature mediates tumor necrosis factor-induced neurovascular lesions in experimental cerebral malaria. 相似文献
104.
105.
Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth. 总被引:2,自引:2,他引:2 下载免费PDF全文
We have previously shown that intranasal infection of mice with mouse hepatitis virus (MHV) strain UAB (MHV-UAB) increases their resistance to Salmonella typhimurium injected intravenously 6 days later. To study how salmonella resistance was induced, BALB/cAnNCr mice were infected with salmonella strains carrying specific genetic alterations. One set of studies compared the effect of MHV infection on subsequent salmonella infections with AroA- (avirulent) and Aro+ (virulent) salmonellae. Unlike its effect on Aro+ salmonellae, MHV failed to reduce the number of AroA- salmonellae recovered from mice. Because AroA- S. typhimurium shows almost no growth in vivo, this failure indicated that the effect of MHV on salmonella resistance required growth of the infecting salmonellae. In other studies, the effect of MHV infection on both growth and killing were monitored simultaneously in mice with growing salmonellae carrying a single copy of the temperature-sensitive pHSG422 plasmid, which is unable to replicate in vivo. MHV infection reduced salmonella growth but caused no increase in salmonella killing. MHV infection of mice given wild-type salmonellae also resulted in no increase in salmonella killing 4 h after salmonella challenge. These studies demonstrate that MHV-UAB infection increases host resistance to salmonellae by enhancing suppression of bacterial growth instead of by increasing the amount of salmonella killing. 相似文献
106.
D. Doyle C. J. Ryan I. S. Benjamin L. H. Blumgart 《International journal of experimental pathology》1978,59(5):461-466
Structural abnormalities are found in the astrocytes of the dentate nuclei of animals after portacaval shunting (PCS). These changes are also found in man in association with portal-systemic encephalopathy. To investigate the relationship between portal-systemic shunting and hepatocellular dysfunction in the pathogenesis of these changes, PCS and protacaval transposition (PCT) were performed in rats. PCT diverts portal blood into the systemic circulation, but retains normal total hepatic blood flow by perfusion with systemic venous blood. Liver function and mass are better preserved than after PCS. Abnormal glial cells were found in 4.03% of animals following sham operation, 13.45% following PCT, and 19.09% following PCS. Both experimental groups differed significantly from control animals, and the number of abnormal cells was significantly higher after PCS than after PCT. These findings are in keeping with the hypothesis that hepatocellular dysfunction plays an important role in addition to portal-systemic shunting in the aetiology of the structural changes in the brain associated with hepatic encephalopathy. 相似文献
107.
Mycobacterium-induced potentiation of type 1 immune responses and protection against malaria are host specific 总被引:2,自引:0,他引:2 下载免费PDF全文
Page KR Jedlicka AE Fakheri B Noland GS Kesavan AK Scott AL Kumar N Manabe YC 《Infection and immunity》2005,73(12):8369-8380
Malaria and tuberculosis are endemic in many regions of the world, and coinfection with the two pathogens is common. In this study, we examined the effects of long- and short-term infection with Mycobacterium tuberculosis on the course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice, which was especially prominent 5 days after infection with P. yoelii 17XL. Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma interferon (IFN-gamma) and tumor necrosis factor alpha than splenocytes from mice infected with either pathogen alone. Interestingly, mycobacterium-induced protection against lethal P. yoelii is mouse strain specific. BALB/c mice were significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL and were not protected against lethal malaria by coinfection with M. tuberculosis. In addition, M. tuberculosis did not augment IFN-gamma responses in BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that M. tuberculosis-induced potentiation of type 1 immune responses is associated with protection against lethal murine malaria. 相似文献
108.
Interaction of Inflammatory Cells and Oral Microorganisms VII. In Vitro Polymorphonuclear Responses to Viable Bacteria and to Subcellular Components of Avirulent and Virulent Strains of Actinomyces viscosus 总被引:1,自引:1,他引:1 下载免费PDF全文
Norton S. Taichman Benjamin F. Hammond Chi-Cheng Tsai Pierre C. Baehni William P. McArthur 《Infection and immunity》1978,21(2):594-604
Both virulent (V) and avirulent (AV) strains of Actinomyces viscosus T14 are capable of colonizing the oral cavity of gnotobiotic rats, but only T14-V causes destructive periodontal disease. The basis for this difference in in vivo pathogenicity has not been adequately defined. In the present study we compared the capacities of T14-AV and T14-V to provoke in vitro extracellular release of lysosomal constituents from human polymorphonuclear leukocytes (PMNs). In serum-free cultures, viable T14-V but not T14-AV stimulated discharge of PMN lysosomes. The release response was correlated with PMN phagocytic activity; thus, PMNs readily ingested T14-V but not T14-AV. To explain these differences in PMN-bacteria interactions, subcellular fractions of T14-AV or T14-V were incubated with PMNs. A crude, insoluble sonic extract derived from T14-V caused PMN lysosome release, but a similar fraction from T14-AV was inactive. However, following extensive washing and treatment with deoxyribonuclease or sodium dodecyl sulfate, cell wall fractions of T14-AV stimulated lysosome release. These procedures apparently removed an extracellular polysaccharide slime which is synthesized by T14-AV but not by T14-V. There was a significant reduction in the capacities of viable T14-V or cell wall fractions of T14-V or T14-AV to provoke PMN lysosome release when these agents were preincubated with a slime material isolated from T14-AV. This inhibitory influence of slime was overcome by the addition of fresh or heated (56°C, 30 min) serum to the PMN-bacteria cultures. The data suggest a relationship between the abilities of the avirulent and virulent strains of A. viscosus T14 to act as periodontal pathogens in vivo and to serve as stimuli for PMN lysosome release in vitro. 相似文献
109.
Lack of cleavage of immunoglobulin A (IgA) from rhesus monkeys by bacterial IgA1 proteases. 总被引:3,自引:1,他引:3 下载免费PDF全文
Bacterial immunoglobulin A1 (IgA1) proteases cleaving IgA1 and secretory IgA1 molecules in the hinge region are believed to be important virulence factors. Previous studies have indicated that IgA of humans, gorillas, and chimpanzees are the exclusive substrates of these enzymes. In a recent study, IgA from the rhesus monkey was found to be susceptible to the IgA1 protease activity of Streptococcus pneumoniae. In an attempt to reproduce this observation, we found that neither five isolates of S. pneumoniae nor other IgA1 protease-producing bacteria representing different cleavage specificities caused cleavage of rhesus monkey IgA. Hence, the rhesus monkey does not appear to be a suitable animal model for studies of IgA1 proteases as virulence factors. 相似文献
110.
Differential cytokine induction by doses of lipopolysaccharide and monophosphoryl lipid A that result in equivalent early endotoxin tolerance. 总被引:3,自引:13,他引:3 下载免费PDF全文
The phenomenon of early endotoxin tolerance, which is induced by sublethal injection of lipopolysaccharide (LPS), results in a protracted period of hyporesponsiveness that is most profound at 3 to 4 days after injection and is marked by reduced cytokine production after a challenge injection of LPS. Early endotoxin tolerance is also induced by the nontoxic LPS derivative monophosphoryl lipid A (MPL), although much more of the monophosphoryl derivative is required to produce a state of tolerance equivalent to that evoked by LPS. In this study, equivalent tolerance-inducing doses of LPS and MPL were tested, and the levels of cytokines induced by LPS and MPL were compared. Although induced levels of colony-stimulating factor were comparable following doses of LPS and MPL that elicited an equivalent state of early endotoxin tolerance, levels of tumor necrosis factor, interleukin-6, and interferon were significantly lower in MPL-injected animals. These results suggest that the lowered toxicity of MPL may be related to its elicitation of significantly lower levels of potentially toxic intermediaries such as tumor necrosis factor, interferon, and interleukin-6. 相似文献