全文获取类型
收费全文 | 7482篇 |
免费 | 433篇 |
国内免费 | 44篇 |
专业分类
耳鼻咽喉 | 86篇 |
儿科学 | 186篇 |
妇产科学 | 179篇 |
基础医学 | 1082篇 |
口腔科学 | 321篇 |
临床医学 | 610篇 |
内科学 | 1294篇 |
皮肤病学 | 116篇 |
神经病学 | 751篇 |
特种医学 | 507篇 |
外科学 | 1126篇 |
综合类 | 34篇 |
一般理论 | 2篇 |
预防医学 | 392篇 |
眼科学 | 204篇 |
药学 | 528篇 |
中国医学 | 14篇 |
肿瘤学 | 527篇 |
出版年
2023年 | 42篇 |
2022年 | 114篇 |
2021年 | 206篇 |
2020年 | 146篇 |
2019年 | 169篇 |
2018年 | 180篇 |
2017年 | 169篇 |
2016年 | 222篇 |
2015年 | 252篇 |
2014年 | 310篇 |
2013年 | 455篇 |
2012年 | 584篇 |
2011年 | 576篇 |
2010年 | 348篇 |
2009年 | 307篇 |
2008年 | 504篇 |
2007年 | 492篇 |
2006年 | 438篇 |
2005年 | 419篇 |
2004年 | 359篇 |
2003年 | 351篇 |
2002年 | 334篇 |
2001年 | 62篇 |
2000年 | 45篇 |
1999年 | 59篇 |
1998年 | 53篇 |
1997年 | 39篇 |
1996年 | 55篇 |
1995年 | 50篇 |
1994年 | 41篇 |
1993年 | 29篇 |
1992年 | 30篇 |
1991年 | 23篇 |
1990年 | 15篇 |
1989年 | 20篇 |
1988年 | 17篇 |
1987年 | 27篇 |
1986年 | 21篇 |
1985年 | 30篇 |
1984年 | 27篇 |
1983年 | 19篇 |
1982年 | 26篇 |
1981年 | 17篇 |
1980年 | 18篇 |
1979年 | 14篇 |
1978年 | 15篇 |
1977年 | 16篇 |
1974年 | 18篇 |
1971年 | 13篇 |
1967年 | 17篇 |
排序方式: 共有7959条查询结果,搜索用时 31 毫秒
31.
Wolenski M Cramer SO Ehrlich S Steeg C Grossschupff G Tenner-Racz K Racz P Fleischer B von Bonin A 《Medical microbiology and immunology》2003,192(4):189-192
CD83 is used as a marker for mature dendritic cells (DC) in man. We have developed a new monoclonal antibody (mAb), Michel-17, that specifically recognizes mouse CD83. We show that murine CD83 is expressed mainly on mature DC and on activated T cells. Histological analysis of serial spleen sections revealed a CD83 expression pattern resembling that of MIDC-8, a known murine DC marker molecule. In contrast to other costimulatory receptors, cross-linking of CD83 with the mAb Michel-17 on DC or T cells does not induce any activation signals. Our data describe for the first time the expression pattern of murine CD83, which is comparable to that of human CD83.The unique mAb Michel-17 will help to elucidate the biological functions of the CD83 molecule in more detail. 相似文献
32.
33.
Papadimitriou GN Dikeos DG Souery D Del-Favero J Massat I Avramopoulos D Blairy S Cichon S Ivezic S Kaneva R Karadima G Lilli R Milanova V Nöthen M Oruc L Rietschel M Serretti A Van Broeckhoven C Stefanis CN Mendlewicz J 《Psychiatric genetics》2003,13(4):211-220
The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder. 相似文献
34.
35.
Cook Graham P.; Meyer Kerstin B.; Neuberger Michael S.; Pettersson Sven 《International immunology》1995,7(1):89-95
The activity of the IgH (Eµ) enhancer in the T lymphocytelineage has been investigated using both transgenic mice andtransfection studies. Thymocyte fractionation experiments indicatethat a transgene consisting of the bacterial chloramphenicolacetyl transferase (CAT) gene, linked to Eµ and the SV40early promoter (Eµ–CAT), is expressed only in thymocyteswith a mature medullary phenotype and not in immature cells.Transfection of this same construct into two thymoma cell linesrepresenting different stages of thymocyte development mimicsthe pattern of activity observed in vivo. Further transfectionexperiments suggest that this pattern of expression might beattributed to the differential activity of the E2E3 and octanucleotidemotifs of Eµ during development. In contrast, an Ig transgene(linked to Eµ and an Ig V promoter) is expressed in themajority of thymocytes. We envisage that the different patternsof expression of the two transgenes reflect interactions betweentheir respective promoters and the factors which are bound toEµ at different stages of thymocyte development. Althoughdiffering in their pattern of expression within the thymus,the two transgenes share the property of extinction in peripheralT lymphocytes. These results indicate that the expression ofEµ-linked transgenes in the thymus cannot simply be explainedby activation of the enhancer in a lymphoid progenitor cellprior to B/T lineage divergence. Rather, the enhancer (or componentsof it) must be independently activated (and inactivated) duringT lymphocyte development. Furthermore, this activity is consistentwith the developmental timing of Ig DH–JH rearrangementsin these cells. 相似文献
36.
Aaron A. Vogan S. Lorena Ament-Velsquez Eric Bastiaans Ola Wallerman Sven J. Saupe Alexander Suh Hanna Johannesson 《Genome research》2021,31(5):789
The genomes of eukaryotes are full of parasitic sequences known as transposable elements (TEs). Here, we report the discovery of a putative giant tyrosine-recombinase-mobilized DNA transposon, Enterprise, from the model fungus Podospora anserina. Previously, we described a large genomic feature called the Spok block which is notable due to the presence of meiotic drive genes of the Spok gene family. The Spok block ranges from 110 kb to 247 kb and can be present in at least four different genomic locations within P. anserina, despite what is an otherwise highly conserved genome structure. We propose that the reason for its varying positions is that the Spok block is not only capable of meiotic drive but is also capable of transposition. More precisely, the Spok block represents a unique case where the Enterprise has captured the Spoks, thereby parasitizing a resident genomic parasite to become a genomic hyperparasite. Furthermore, we demonstrate that Enterprise (without the Spoks) is found in other fungal lineages, where it can be as large as 70 kb. Lastly, we provide experimental evidence that the Spok block is deleterious, with detrimental effects on spore production in strains which carry it. This union of meiotic drivers and a transposon has created a selfish element of impressive size in Podospora, challenging our perception of how TEs influence genome evolution and broadening the horizons in terms of what the upper limit of transposition may be.Transposable elements (TEs) are major agents of change in eukaryotic genomes. Their ability to selfishly parasitize their host replication machinery has large impacts on both genome size and on gene regulation (Chénais et al. 2012). In extreme cases, TEs can contribute up to 85% of genomic content (Schnable et al. 2009), and expansion and reduction of TEs can result in rapid changes in both genome size and architecture (Haas et al. 2009; Möller and Stukenbrock 2017; Talla et al. 2017). Generally, TEs have small sizes (∼50–12,000 bp) and accomplish these large-scale changes through their sheer number. For example, there are ∼1.1 million Alu elements in the human genome, which have had a large impact on genome evolution (Jurka 2004; Bennett et al. 2008). The largest known cases among Class I retrotransposons are long terminal repeat (LTR) elements that can be as large as 30 kb, but among Class II DNA transposons, Mavericks/Polintons are known to grow as large as 40 kb through the capture of additional open reading frames (ORFs) (Arkhipova and Yushenova 2019). Recently, a behemoth TE named Teratorn was described in teleost fish; it can be up to 182 kb in length, dwarfing all other known TEs. Teratorn has achieved this impressive size by fusing a piggyBac DNA transposon with a herpesvirus, thereby blurring the line between TEs and viruses (Inoue et al. 2017, 2018). Truly massive transposons may be lurking in the depths of many eukaryotic genomes, but the limitations of short-read genome sequencing technologies and the lack of population-level high-quality assemblies may make them difficult to identify.The Spok block is a large genomic feature that was first identified thanks to the presence of the spore killing (Spok) genes in species from the genus Podospora (Grognet et al. 2014; Vogan et al. 2019). The Spoks are selfish genetic elements that bias their transmission to the next generation in a process known as meiotic drive. Here, drive occurs by inducing the death of spores that do not inherit them, through a single protein that operates as both a toxin and an antidote (Grognet et al. 2014; Vogan et al. 2019). The first Spok gene described, Spok1, was discovered in Podospora comata (Grognet et al. 2014). In P. anserina, the homologous gene Spok2 is found at high population frequencies, whereas two other genes of the Spok family, Spok3 and Spok4, are at low to intermediate frequencies (Vogan et al. 2019). Unlike Spok1 and Spok2, however, Spok3 and Spok4 are always associated with a large genomic region (the Spok block). The Spok block can be located at different chromosomal locations in different individuals but is never found more than once in natural strains. The number of Spok genes and the location of the Spok block (which carries Spok3, Spok4, or both) define the overall meiotic driver behavior of a given genome, which can be classified into the so-called Podospora spore killers or Psks (van der Gaag et al. 2000; Vogan et al. 2019). The Spok block stands out not only because of its size, typically around 150 kb, but also because there is otherwise high genome collinearity among strains of P. anserina and with the related species P. comata and P. pauciseta (Vogan et al. 2019).The fact that the Spok block is found at unique genomic positions between otherwise highly similar strains is of prime interest as each novel Spok block position creates a unique meiotic drive type (Psk) due to the intricacies of meiosis in Podospora (Vogan et al. 2019). We therefore set out to determine the mechanism through which the Spok block relocates throughout the genome. Additionally, we annotated the gene content of the various Spok blocks to describe their composition and understand what represents the minimal component of the Spok block. Lastly, we conducted fitness assays to investigate whether the presence of the Spok block imparts any detrimental effects upon the host. 相似文献
37.
38.
The occurrence of antibodies to human C-reactive protein (CRP) was analysed by enzyme-linked immunosorbent assay (ELISA) in 56 patient sera known to contain antibodies to double-stranded DNA (dsDNA) and in 16 sera from patients with primary Sj?gren's syndrome (SS), 15 rheumatoid arthritis, 31 Crohn's disease, and 37 ulcerative colitis. Eighty-seven per cent of the patients with anti-dsDNA antibodies had systemic lupus erythematosus (SLE) and the remaining had autoimmune hepatitis. The cut-off for positive anti-CRP test was set at the 95th percentile of 100 healthy blood donors. Twenty of 56 anti-dsDNA sera (36%) and two of 16 SS sera (13%) had antibodies reactive with human CRP, whereas all other samples were negative. Thirteen of 27 SLE patients (48%) were positive on at least one occasion. The sera containing anti-CRP antibodies only reacted with surface-bound antigen, but not with native CRP in solution. In conclusion, we found that autoantibodies to CRP are common in sera from patients with anti-dsDNA antibodies. It is not likely that this explains the relative failure of CRP response in patients with active SLE. However, it cannot be excluded that anti-CRP autoantibodies have other biological potentials of pathophysiological interest in SLE, for instance by binding to CRP deposited on cell and tissue surfaces. 相似文献
39.
Pettersson F Vogt AM Jonsson C Mok BW Shamaei-Tousi A Bergström S Chen Q Wahlgren M 《Infection and immunity》2005,73(11):7736-7746
The occlusion of vessels by packed Plasmodium falciparum-infected (iRBC) and uninfected erythrocytes is a characteristic postmortem finding in the microvasculature of patients with severe malaria. Here we have employed immunocompetent Sprague-Dawley rats to establish sequestration in vivo. Human iRBC cultivated in vitro and purified in a single step over a magnet were labeled with 99mtechnetium, injected into the tail vein of the rat, and monitored dynamically for adhesion in the microvasculature using whole-body imaging or imaging of the lungs subsequent to surgical removal. iRBC of different lines and clones sequester avidly in vivo while uninfected erythrocytes did not. Histological examination revealed that a multiadhesive parasite adhered in the larger microvasculature, inducing extensive intravascular changes while CD36- and chondroitin sulfate A-specific parasites predominantly sequester in capillaries, inducing no or minor pathology. Removal of the adhesive ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), preincubation of the iRBC with sera to PfEMP1 or preincubation with soluble PfEMP1-receptors prior to injection significantly reduced the sequestration. The specificity of iRBC binding to the heterologous murine receptors was confirmed in vitro, using primary rat lung endothelial cells and rat lung cryosections. In offering flow dynamics, nonmanipulated endothelial cells, and an intact immune system, we believe this syngeneic animal model to be an important complement to existing in vitro systems for the screening of vaccines and adjunct therapies aiming at the prevention and treatment of severe malaria. 相似文献
40.
nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma 总被引:18,自引:0,他引:18
Kapitanović S Cacev T Berković M Popović-Hadzija M Radosević S Seiwerth S Spaventi S Pavelić K Spaventi R 《Journal of clinical pathology》2004,57(12):1312-1318
BACKGROUND: The discovery that genetic alterations in oncogenes and tumour suppressor genes accompany tumour formation in many human tumours has encouraged the search for genes that promote or suppress tumour spread and metastasis; nm23 is a promising candidate for a metastasis suppressing gene.AIMS: To evaluate whether expression of nm23-H1 protein or loss of heterozygosity (LOH) of the nm23-H1 gene is associated with colon cancer progression. MATERIALS/METHODS: Paraffin wax embedded tissue sections were analysed immunohistochemically. DNA isolated from normal and tumour tissue was used for LOH analysis using a variable nucleotide tandem repeat (VNTR) marker located in the untranslated 5' region of the nm23-H1 gene. RNA isolated from tumour and normal tissue was used for "real time" RT-PCR. RESULTS: Of 102 adenocarcinomas examined, 58.8% stained weakly for nm23-H1 protein. There was a negative correlation between nm23-H1 positivity and tumour histological grade. In VNTR analysis, 70.2% of patients were informative and 27.4% of tumours had nm23-H1 LOH. There was a positive correlation between nm23-H1 LOH and both tumour histological grade and Dukes's stage. Expression of nm23-H1 mRNA was increased in 22 of 30 colon tumours compared with normal tissue. No significant correlation was found between nm23-H1 mRNA expression and histological grade or Dukes's stage of tumours. CONCLUSIONS: These findings suggest that nm23-H1 protein expression in early stages may have a role in suppressing metastasis in sporadic colon cancer, whereas at a later stage both reduced nm23-H1 protein expression and LOH of the nm23-H1 gene may play role in colon cancer progression and metastasis. 相似文献