全文获取类型
收费全文 | 1881篇 |
免费 | 202篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 43篇 |
妇产科学 | 15篇 |
基础医学 | 416篇 |
口腔科学 | 56篇 |
临床医学 | 210篇 |
内科学 | 368篇 |
皮肤病学 | 26篇 |
神经病学 | 204篇 |
特种医学 | 122篇 |
外科学 | 192篇 |
综合类 | 40篇 |
预防医学 | 162篇 |
眼科学 | 21篇 |
药学 | 147篇 |
中国医学 | 1篇 |
肿瘤学 | 53篇 |
出版年
2021年 | 35篇 |
2020年 | 13篇 |
2019年 | 18篇 |
2018年 | 21篇 |
2016年 | 24篇 |
2015年 | 25篇 |
2014年 | 40篇 |
2013年 | 59篇 |
2012年 | 79篇 |
2011年 | 82篇 |
2010年 | 62篇 |
2009年 | 46篇 |
2008年 | 74篇 |
2007年 | 108篇 |
2006年 | 71篇 |
2005年 | 59篇 |
2004年 | 74篇 |
2003年 | 62篇 |
2002年 | 47篇 |
2001年 | 53篇 |
2000年 | 46篇 |
1999年 | 55篇 |
1998年 | 43篇 |
1997年 | 47篇 |
1996年 | 34篇 |
1995年 | 30篇 |
1994年 | 31篇 |
1993年 | 48篇 |
1992年 | 37篇 |
1991年 | 33篇 |
1990年 | 42篇 |
1989年 | 42篇 |
1988年 | 46篇 |
1987年 | 37篇 |
1986年 | 47篇 |
1985年 | 39篇 |
1984年 | 27篇 |
1983年 | 21篇 |
1982年 | 21篇 |
1981年 | 21篇 |
1980年 | 29篇 |
1979年 | 18篇 |
1977年 | 23篇 |
1976年 | 18篇 |
1975年 | 17篇 |
1974年 | 18篇 |
1973年 | 15篇 |
1972年 | 20篇 |
1971年 | 19篇 |
1969年 | 19篇 |
排序方式: 共有2091条查询结果,搜索用时 0 毫秒
11.
Rapid leukocyte integrin activation by chemokines 总被引:12,自引:0,他引:12
Carlo Laudanna Ji Yun Kim Gabriela Constantin Eugene C. Butcher 《Immunological reviews》2002,186(1):37-46
Summary: Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside-out signal transduction pathways leading to integrin-dependent adhesion. Integrin activation by chemokines is very rapid, is downmodulated within minutes and appears to involve both enhanced heterodimer lateral mobility on the plasma membrane, facilitating encounters with dispersed ligand, as well as induction of a high-affinity state. These two modalities of integrin activation by chemokines involve distinct signaling pathways in the cell, yet complement each other functionally, allowing binding of rolling cells under conditions of low as well as high ligand density. Recent data show that chemokines generate both pro- and anti-adhesive intracellular signaling events, whose equilibrium is likely to be relevant to the kinetics of adhesion and de-adhesion, and to cell movement during diapedesis and chemotaxis. Importantly, chemokines utilize different signaling mechanisms to modulate the activity of distinct integrin subtypes. These recent advances suggest that chemokines may regulate adhesive responses of immune cells based not only on patterns of chemokine receptor expression, but also on variable signaling pathways that can modulate the pro-adhesive responses of leukocytes as a function of their differentiated state, and of the local microenvironment. 相似文献
12.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
13.
Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes. 总被引:17,自引:0,他引:17
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Eric J Kunkel Judie Boisvert Kristine Murphy Mark A Vierra Mark C Genovese Andrew J Wardlaw Harry B Greenberg Martin R Hodge Lijun Wu Eugene C Butcher James J Campbell 《The American journal of pathology》2002,160(1):347-355
Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4(+) lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4(+) populations in blood, as well as by tissue-infiltrating lymphocytes from a number of sites. To characterize the similarities and differences among tissue-infiltrating lymphocytes, and to shed light on the specialization of lymphocyte subsets that mediate inflammation and immune surveillance in particular tissues, we have examined the expression of CCR4, CXCR3, and CCR5 on CD4(+) lymphocytes directly isolated from a wide variety of normal and inflamed tissues. Extra-lymphoid tissues contained only memory lymphocytes, many of which were activated (CD69(+)). As predicted by classical studies, skin lymphocytes were enriched in CLA expression whereas intestinal lymphocytes were enriched in alpha(4)beta(7) expression. CCR4 was expressed at high levels by skin-infiltrating lymphocytes, at lower levels by lung and synovial fluid lymphocytes, but never by intestinal lymphocytes. Only the high CCR4 levels characteristic of skin lymphocytes were associated with robust chemotactic and adhesive responses to TARC, consistent with a selective role for CCR4 in skin lymphocyte homing. In contrast, CXCR3 and CCR5 were present on the majority of lymphocytes from each non-lymphoid tissue examined, suggesting that these receptors are unlikely to determine tissue specificity, but rather, may play a wider role in tissue inflammation. 相似文献
14.
Free malarial merozoites isolated from in vitro cultures of P. knowlesi and emulsified with Freund's complete (FCA) or incomplete (FIA) adjuvant were used to vaccinate twelve Rhesus monkeys against the uniformly lethal infection caused by P. knowlesi. Initial challenge of six monkeys with the same parasite variant as used for vaccination produced no detectable infection in three monkeys, while three others developed low-grade parasitaemia (maximum 1.5 per cent), which terminated after 6-11 days. Vaccination with merozoites in either FCA or FIA induced protection against homologous variant challenge. Six other monkeys were challenged first with a parasite variant different from that used for vaccination. Two animals immunized with merozoites in FIA alone or in FCA on only one occasion developed fatal infections. The other four animals vaccinated at least twice with merozoites in FCA showed low-grade parasitaemia (maximum 1.5 per cent) which terminated after 8-12 days. Eight monkeys rechallenged on eleven occasions at intervals of up to 16 weeks were completely resistant to several variants and a distinct laboratory strain of P. knowlesi, but developed chronic malaria similar to that in unimmunized controls when challenged with a different species of malaria, P. cynomolgi bastianellii. It is concluded that merozoite vaccination of Rhesus monkeys induces immunity against the erythrocyte stages of P. knowlesi far greater in degree and significantly broader in variant specificity than that achieved by previous methods of immunization or by repeated drug-controlled infections. 相似文献
15.
ICAM-1, VCAM-1, and MAdCAM-1 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro. 总被引:4,自引:2,他引:4
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
B. J. Steffen G. Breier E. C. Butcher M. Schulz B. Engelhardt 《The American journal of pathology》1996,148(6):1819-1838
The expression of cell adhesion molecules (CAMs) in the choroid plexus was studied in normal brain and during experimental autoimmune encephalomyelitis (EAE) in the SJL/J mouse during inflammation induced by intracerebral injection of killed Corynebacterium parvum in the C3H/He mouse. Both ICAM-1 and VCAM-1, but not MAdCAM-1, were constitutively expressed on choroid plexus epithelium but not on the fenestrated capillary endothelial cells within the choroid plexus. During EAE, we observed an up-regulation of ICAM-1 and VCAM-1 and de novo expression of MAdCAM-1 on choroid plexus epithelial cells. In contrast, endothelial cells in the choroid plexus were not induced to express any of the investigated CAMs. In in situ hybridization analysis we demonstrated that ICAM-1, VCAM-1, and MAdCAM-1 were locally synthesized and that the amount of their mRNAs increased in the inflamed choroid plexus. In vitro, primary choroid plexus epithelial cells could be induced to express ICAM-1, VCAM-1, and MAdCAM-1 on their surface after treatment with proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, interferon-gamma, and lipopolysaccharide. To investigate the functional status of the expressed CAMs we performed Stamper-Woodruff binding assays on frozen sections of inflamed and naive brains. ICAM-1, VCAM-1, and MAdCAM-1 expressed in choroid plexus epithelial cells mediated binding of lymphocytes via their known ligands LFA-1 and alpha4-integrin, respectively. The expression of ICAM-1, VCAM-1, and MAdCAM-1 on choroid plexus epithelial cells together with the lack of their expression on the fenestrated choroid plexus endothelium raises the possibility that the epithelial blood-cerebrospinal-fluid barrier plays an important role in the immunosurveillance of the central nervous system. 相似文献
16.
Performance of the COBAS AMPLICOR HCV MONITOR test, version 2.0, an automated reverse transcription-PCR quantitative system for hepatitis C virus load determination
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Gerken G Rothaar T Rumi MG Soffredini R Trippler M Blunk MJ Butcher A Soviero S Colucci G 《Journal of clinical microbiology》2000,38(6):2210-2214
17.
Detection of human immunodeficiency virus type 1 (HIV-1) DNA and RNA sequences in HIV-1 antibody-positive blood donors in Uganda by the Roche AMPLICOR assay.
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J B Jackson E M Piwowar J Parsons P Kataaha G Bihibwa J Onecan S Kabengera S D Kennedy A Butcher 《Journal of clinical microbiology》1997,35(4):873-876
The ability of commercially available PCR-based assays to accurately detect or quantitate human immunodeficiency virus type 1 (HIV-1) DNA or RNA in individuals predominantly infected with HIV-1 subtypes A and D is not known. Therefore, peripheral leukocytes from 43 individuals in Kampala, Uganda, positive for HIV by the Western blot (immunoblot) assay were tested by using the Roche AMPLICOR HIV-1 assay for the detection of DNA gag sequences. Plasma from these same individuals was tested by using the Roche HIV-1 AMPLICOR MONITOR HIV-1 assay for the quantitation of HIV-1 RNA gag sequences. In addition, peripheral leukocytes were tested for HIV-1 DNA by using a lower annealing temperature or a different primer pair for the HIV-1 pol region. The proportions of individuals with detectable HIV-1 DNA and RNA gag sequences by the Roche assays were 74 and 90%, respectively. The proportions positive for HIV-1 DNA sequences by using a 50 degrees C annealing temperature or the pol primer pair were 71 and 98%, respectively. In summary, the standard Roche assay did not detect HIV-1 DNA sequences in a significant number of HIV-1-infected individuals in Uganda. However, use of a pol primer pair increased the sensitivity of the assay to 98%. The sensitivity of the Roche AMPLICOR MONITOR assay for the detection and quantitation of HIV-1 RNA sequences was significantly higher than that of the DNA-based assay, but the efficiency of the assay, and hence, the accuracy of the values obtained with RNA, is not known. Modifications to existing assays are needed to enhance the sensitivities and accuracies of these commercially available assays for use in developing countries where non-B HIV-1 subtypes predominate. 相似文献
18.
Laura Cau Michael R. Williams Anna M. Butcher Teruaki Nakatsuji Jeffrey S. Kavanaugh Joyce Y. Cheng Faiza Shafiq Kyle Higbee Tissa R. Hata Alexander R. Horswill Richard L. Gallo 《The Journal of allergy and clinical immunology》2021,147(3):955-966.e16
- Download : Download high-res image (400KB)
- Download : Download full-size image
19.
20.
Marianne Quiding-Jrbrink Mekuria Lakew Inger Nordstrm Jacques Banchereau Eugene Butcher Jan Holmgren Cecil Czerkinsky 《European journal of immunology》1995,25(2):322-327
Circulating spontaneous antibody-secreting cells (ASC) induced by mucosal and systemic immunizations in human volunteers have been characterized with respect to differentiation stage and homing commitments. Irrespective of the immunization route, the large majority of ASC co-expressed CD19 and HLA-DR, which are normally lost during the transition of plasmablasts to plasmocytes, as well as CD38, a marker of activated B cell blasts, expressed also by plasmocytes. However, these cells expressed neither CD28, a molecule acquired by plasmocytes, nor CD22 and CD37, which are lost during the transition of plasmablasts to plasmocytes. Therefore, the large majority of ASC found in peripheral blood after oral and parenteral immunizations are terminally differentiated B cells, but not fully differentiated plasmocytes. As a whole, the mucosally derived ASC population seemed to be more homogenously differentiated. CD25 was detected on few ASC, whereas ASC expressing CD71 were more numerous, especially among systemically derived ASC. Almost all ASC expressed the adhesion molecules CD44 and α4-integrins, irrespective of immunization route. However, virtually all systemically derived ASC expressed L-selectin, recognizing the peripheral lymph node addressin, whereas only a minority of mucosally induced blood ASC expressed L-selectin. These studies are the first to demonstrate in humans that circulating precursors of mucosal B cell immunoblasts utilize organ-specific recognition mechanisms distinct from those of corresponding systemic B cells and appear to be more advanced in the B lineage maturation pathway. Specialization of receptor expression could explain both the unification of immune responses in diverse mucosal sites and the physiologic segregation of mucosal from non-mucosal immune mechanisms in humans. 相似文献