全文获取类型
收费全文 | 3870篇 |
免费 | 243篇 |
国内免费 | 33篇 |
专业分类
耳鼻咽喉 | 26篇 |
儿科学 | 144篇 |
妇产科学 | 158篇 |
基础医学 | 416篇 |
口腔科学 | 304篇 |
临床医学 | 315篇 |
内科学 | 895篇 |
皮肤病学 | 88篇 |
神经病学 | 165篇 |
特种医学 | 175篇 |
外科学 | 367篇 |
综合类 | 143篇 |
一般理论 | 1篇 |
预防医学 | 379篇 |
眼科学 | 86篇 |
药学 | 302篇 |
1篇 | |
中国医学 | 88篇 |
肿瘤学 | 93篇 |
出版年
2023年 | 31篇 |
2022年 | 64篇 |
2021年 | 101篇 |
2020年 | 81篇 |
2019年 | 81篇 |
2018年 | 109篇 |
2017年 | 94篇 |
2016年 | 104篇 |
2015年 | 108篇 |
2014年 | 153篇 |
2013年 | 152篇 |
2012年 | 242篇 |
2011年 | 246篇 |
2010年 | 154篇 |
2009年 | 127篇 |
2008年 | 164篇 |
2007年 | 194篇 |
2006年 | 149篇 |
2005年 | 96篇 |
2004年 | 120篇 |
2003年 | 79篇 |
2002年 | 98篇 |
2001年 | 58篇 |
2000年 | 50篇 |
1999年 | 52篇 |
1998年 | 58篇 |
1997年 | 66篇 |
1996年 | 60篇 |
1995年 | 50篇 |
1994年 | 64篇 |
1993年 | 43篇 |
1992年 | 31篇 |
1991年 | 32篇 |
1990年 | 28篇 |
1989年 | 37篇 |
1988年 | 32篇 |
1987年 | 39篇 |
1986年 | 38篇 |
1985年 | 23篇 |
1984年 | 24篇 |
1983年 | 19篇 |
1982年 | 17篇 |
1981年 | 28篇 |
1980年 | 19篇 |
1959年 | 35篇 |
1958年 | 58篇 |
1957年 | 87篇 |
1956年 | 45篇 |
1955年 | 75篇 |
1954年 | 67篇 |
排序方式: 共有4146条查询结果,搜索用时 15 毫秒
31.
Lipids from Mycobacterium leprae cell wall are endowed with an anti-inflammatory property and inhibit macrophage function in vivo.
下载免费PDF全文
![点击此处可从《Immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In general, the majority of bacteria are pre-inflammatory when injected in experimental animals. However, Mycobacterium leprae has no inflammatory effect when injected into mouse footpad, but using the delipidated mycobacteria we observed a mild significant increase in footpad oedema. Other mycobacteria, Mycobacterium bovis-BCG or M. tuberculosis induce a strong paw oedema. Furthermore, M. leprae reduced locally the BCG-induced inflammatory reaction in mouse footpad, whereas delipidated M. leprae did not influence this reaction. Both M. leprae and M. leprae cell wall lipids blocked immune phagocytosis in vivo by inflammatory macrophages (from an induced focus). In contrast delipidated M. leprae stimulated the phagocytosis reaction. Neither intact M. leprae. delipidated M. leprae, nor its lipids had any toxic effect on macrophages or on cell migration. Although M. leprae did not interfere on cell influx and cell type in an induced-inflammatory site, this mycobacterium led to the appearance of a distinct cell population in vivo. The hypothesis is that M. leprae would transform macrophages in epithelioid cells, suggested by morphology analysis of cells by fluorescence-activated cell sorter and observed under optic microscopy. 相似文献
32.
Astrid LA. Kuijpers Rolph Pfundt Patrick LJM Zeeuwen Henri OF. Molhuizen Edwin CM. Mariman Peter CM. van de Kerkhof Joost Schalkwijk 《Clinical genetics》1998,54(1):96-101
Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear leukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known as elafin, is a potent inhibitor of human leukocyte elastase and proteinase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein level, SKALP is significantly decreased in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis. This finding raised the possibility that SKALP could be one of the candidate genes for pustular forms of psoriasis. We therefore performed single strand conformation polymorphism (SSCP) analysis on the SKALP gene to screen for mutations/polymorphisms in the exons of 30 patients with plaque-type psoriasis, 15 patients with pustular psoriasis and 48 healthy controls. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threonine for alanine in the signal peptide. In the promoter region a dinucleotide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that there is no allelic association between pustular psoriasis and SKALP gene polymorphisms. 相似文献
33.
The functional of B-L (Ia-equivalent)-positive (B-L+) adn -negative (B-L-) chicken peripheral blood lymphocytes (PBL) was studied in vitro and in vivo. The PBL were first stained in direct immunofluorescence tests with a fluorescein isothiocyanate-labelled anti-B-L alloantiserum and then separated by means of a fluorescence-activated cell sorter. In agreement with our previous findings, B-L- cells showed functional properties of T lymphocytes, responding to concanavalin A and phytohaemagglutinin-P in vitro and inducing a graft-versus-host (GVH) reaction when injected into allogeneic embryos. Sorted B-L+ gave no responses in any of these assays. Neither B-L+ nor B-L- cells, when tested alone, responded significantly to pokeweed mitogen, but mixtures of the two restored the responsiveness to that of the original unsorted suspension. Of the B-L+ PBL, 10% were T cells, which may account for the low GVH reactivity given by this population. 相似文献
34.
bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors 总被引:16,自引:0,他引:16
Proliferative expansion and apoptotic cell death play prominent roles in T
cell development. The molecular control of cell cycle progression and
apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit
apoptosis and slow cell cycle progression in cortical thymocytes and mature
T cells, particularly during the transition from the quiescent state into
the cell cycle. Here the impact of bcl-2 transgene expression on
CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival
of these progenitors at all of the four major differentiation stages, CD25-
CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and
CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover
only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice
expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene
we conclude that Bcl-2 inhibits proliferation only of T cell progenitors
that are activated via the pre- TCR, not those stimulated via c-Kit and the
IL-7 receptor.
相似文献
35.
36.
JUAN C. DE LA TORRE MARGARET MALLORY MICHELLE BROT LISA GOLD GEORGE KOOB MICHAEL B. A. OLDSTONE ELIEZER MASLIAH 《Virology》1996,220(2):508
Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection bothin vitroandin vivoselectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury. 相似文献
37.
High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes 总被引:5,自引:0,他引:5
Shuber AP; Michalowsky LA; Nass GS; Skoletsky J; Hire LM; Kotsopoulos SK; Phipps MF; Barberio DM; Klinger KW 《Human molecular genetics》1997,6(3):337-347
As more mutations are identified in genes of known sequence, there is a
crucial need in the areas of medical genetics and genome analysis for
rapid, accurate and cost-effective methods of mutation detection. We have
developed a multiplex allele-specific diagnostic assay (MASDA) for analysis
of large numbers of samples (> 500) simultaneously for a large number of
known mutations (> 100) in a single assay. MASDA utilizes
oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA
samples are immobilized on a solid support and a single hybridization is
performed with a pool of allele-specific oligonucleotide (ASO) probes. Any
probes complementary to specific mutations present in a given sample are in
effect affinity purified from the pool by the target DNA. Sequence-specific
band patterns (fingerprints), generated by chemical or enzymatic sequencing
of the bound ASO(s), easily identify the specific mutation(s). Using this
design, in a single diagnostic assay, we tested samples for 66 cystic
fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell
anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations,
four mutations in Canavan disease, four mutations in Fanconi anemia, and
five mutations in BRCA1. Each mutation was correctly identified. Finally,
in a blinded study of 106 of these mutations in > 500 patients, all
mutations were properly identified. There were no false positives or false
negatives. The MASDA assay is capable of detecting point mutations as well
as small insertion or deletion mutations. This technology is amenable to
automation and is suitable for immediate utilization for high-throughput
genetic diagnostics in clinical and research laboratories.
相似文献
38.
Ana Grangeia Miguel Leão Carla P. Moura 《American journal of medical genetics. Part A》2020,182(1):25-28
Wiedemann‐Steiner syndrome (WSS) is a rare genetic disorder characterized by growth retardation, facial dysmorphism, hypertrichosis cubiti and neurodevelopment delay. It is caused by pathogenic variants in the KMT2A gene. This report describes two unrelated Portuguese patients, age 11 and 17 years, with a phenotype concordant with WSS and clinical and molecular diagnosis of WSS by the identification of two novel frameshift variants in the KMT2A gene. This work also highlights the presence of certain clinical features in patients with growth retardation and development delay and should draw attention to the diagnosis of WSS, when hirsutism, particularly hypertrichosis cubiti is present. 相似文献
39.
40.
Delivery of a hammerhead ribozyme specifically down-regulates the production of fibrillin-1 by cultured dermal fibroblasts 总被引:4,自引:1,他引:4
Kilpatrick MW; Phylactou LA; Godfrey M; Wu CH; Wu GY; Tsipouras P 《Human molecular genetics》1996,5(12):1939-1944
The hammerhead ribozyme is a small catalytic RNA molecule. Potential
hammerhead ribozymes that possess a catalytic domain and flanking sequence
complementary to a target mRNA can cleave in trans at a putative cleavage
site within the target molecule. We have investigated the potential of
hammerhead ribozymes to down-regulate the product of the fibrillin-1 gene
(FBN1). Fibrillin is a 347 kDa glycoprotein that is a major constituent of
the elastin-associated microfibrils. Mutations in the FBN1 gene are
responsible for Marfan syndrome (MFS), a common systemic disorder of the
connective tissue. Many FBN1 mutations responsible for MFS appear to act in
a dominant-negative fashion, raising the possibility that reduction of the
amount of product from the mutant FBN1 allele might be a valid therapeutic
approach for MFS. A trans-acting hammerhead ribozyme (FBN1-RZ1) targeted to
the 5' end of the human FBN1 mRNA has been designed and synthesized, and
shown to cleave its target efficiently in vitro. FBN1-RZ1 cleavage is
magnesium dependent and efficient at both 37 and 50 degrees C. Delivery of
the FBN1-RZ1 ribozyme into cultured dermal fibroblasts, by receptor-
mediated endocytosis of a ribozyme-transferrin-polylysine complex,
specifically reduces both cellular FBN1 mRNA and the deposition of
fibrillin in the extracellular matrix. These results suggest that the use
of hammerhead ribozymes is a valid approach to the study of fibrillin gene
expression and possibly to the development of a therapeutic approach to
MFS.
相似文献