全文获取类型
收费全文 | 4896篇 |
免费 | 357篇 |
国内免费 | 23篇 |
专业分类
耳鼻咽喉 | 17篇 |
儿科学 | 240篇 |
妇产科学 | 83篇 |
基础医学 | 597篇 |
口腔科学 | 128篇 |
临床医学 | 471篇 |
内科学 | 876篇 |
皮肤病学 | 76篇 |
神经病学 | 501篇 |
特种医学 | 535篇 |
外科学 | 588篇 |
综合类 | 70篇 |
一般理论 | 3篇 |
预防医学 | 421篇 |
眼科学 | 33篇 |
药学 | 276篇 |
中国医学 | 3篇 |
肿瘤学 | 358篇 |
出版年
2022年 | 31篇 |
2021年 | 52篇 |
2020年 | 49篇 |
2019年 | 54篇 |
2018年 | 73篇 |
2017年 | 40篇 |
2016年 | 75篇 |
2015年 | 88篇 |
2014年 | 106篇 |
2013年 | 150篇 |
2012年 | 162篇 |
2011年 | 206篇 |
2010年 | 165篇 |
2009年 | 152篇 |
2008年 | 163篇 |
2007年 | 163篇 |
2006年 | 161篇 |
2005年 | 129篇 |
2004年 | 126篇 |
2003年 | 142篇 |
2002年 | 131篇 |
2001年 | 121篇 |
2000年 | 142篇 |
1999年 | 100篇 |
1998年 | 159篇 |
1997年 | 148篇 |
1996年 | 179篇 |
1995年 | 117篇 |
1994年 | 92篇 |
1993年 | 104篇 |
1992年 | 118篇 |
1991年 | 123篇 |
1990年 | 111篇 |
1989年 | 137篇 |
1988年 | 115篇 |
1987年 | 123篇 |
1986年 | 126篇 |
1985年 | 115篇 |
1984年 | 77篇 |
1983年 | 75篇 |
1982年 | 59篇 |
1981年 | 36篇 |
1980年 | 58篇 |
1979年 | 62篇 |
1978年 | 38篇 |
1977年 | 41篇 |
1976年 | 41篇 |
1975年 | 43篇 |
1974年 | 23篇 |
1971年 | 28篇 |
排序方式: 共有5276条查询结果,搜索用时 15 毫秒
51.
Long-term in vivo depletion of functional CD4+ T lymphocytes from calves requires both thymectomy and anti-CD4 monoclonal antibody treatment 下载免费PDF全文
In vivo depletion of lymphocyte subsets is a direct approach used for dissection of the mechanisms of protective immunity. Long-term in vivo depletion of bovine T lymphocyte subpopulations with monoclonal antibody (mAb) treatment alone has been difficult to achieve. The objective of this study was to determine whether both thymectomy and anti-CD4 mAb treatment would optimize long-term in vivo depletion of functional bovine CD4+ T lymphocytes. Calves were thymectomized and treated with high doses of anti-CD4 mAb (approximately 5 mg/kg) over 4 days followed by subsequent lower doses (approximately 0.3 mg/kg) administered twice weekly for an additional 7 weeks. Depletion of CD4+ T lymphocytes from blood, spleen and peripheral lymph nodes was significantly improved in thymectomized calves compared to thymus-intact anti-CD4 mAb-treated calves. Significant differences in percentages of CD4+ T lymphocytes between thymectomized and thymus-intact calves were sustained for the duration of the 8-week study. Depletion of CD4+ T lymphocytes from thymectomized calves resulted in complete abrogation of lymphoproliferative responses to ovalbumin. In addition, thymectomized calves treated with anti-CD4 mAb had significantly reduced immunoglobulin G1 and no detectable immunoglobulin G2 ovalbumin-specific antibody responses compared to thymus-intact anti-CD4 mAb-treated calves. The results of this study demonstrate that both thymectomy and treatment with anti-CD4 mAb are required for long-term in vivo depletion of functional bovine CD4+ T lymphocytes. 相似文献
52.
Immune responses of goats persistently infected with caprine arthritis-encephalitis virus. 总被引:3,自引:3,他引:3 下载免费PDF全文
D S Adams T B Crawford K L Banks T C McGuire L E Perryman 《Infection and immunity》1980,28(2):421-427
Eight cesarean-derived goat kids were inoculated with caprine arthritis-encephalitis virus (CAEV), and proliferative responses of their peripheral blood mononuclear cells to mitogens and CAEV antigen were monitored for 9 months. Antibody specific for CAEV was measured by an enzyme-linked immunosorbent assay. Five cesarean-derived noninfected goats were tested simultaneously. Significant differences between the infected and control mononuclear cell proliferation reactions to CAEV began 14 days post-inoculation and continued in a fluctuant manner until 134 days post-inoculation. The magnitude of the proliferative reaction steadily increased in infected goats until the end of the experiment at 271 days post-inoculation. Responses to mitogens were not significantly different between infected and control goats. Virus-inoculated goats produced CAEV-specific antibody that reached a maximum level between 49 and 77 days post-inoculation and then declined to lower levels through 271 days post-inoculation. The virus-inoculated goats developed mild but characteristic clinical evidence of caprine arthritis-encephalitis, and CAEV was reisolated from four goats at 286 days post-inoculation. The five control goats developed neither an anti-CAEV immune response nor clinical disease, and CAEV could not be reisolated from them. 相似文献
53.
Staska LM Davies CJ Brown WC McGuire TC Suarez CE Park JY Mathison BA Abbott JR Baszler TV 《Infection and immunity》2005,73(3):1321-1329
Previously, our laboratory showed that Holstein cattle experimentally infected with Neospora caninum develop parasite-specific CD4+ cytotoxic T lymphocytes (CTL) that lyse infected, autologous target cells through a perforin-granzyme pathway. To identify specific parasite antigens inducing bovine CTL and helper T-lymphocyte responses for vaccine development against bovine neosporosis, the tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-gamma) secretion, while recombinant NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope-bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the entire NcSRS2 sequence. Four experimentally infected cattle with six different major histocompatibility complex (MHC) class II haplotypes were the source of immune cells used to identify NcSRS2 peptides presented by Holstein MHC haplotypes. NcSRS2 peptides were mapped by using IFN-gamma secretion by rNcSRS2-stimulated, short-term T-lymphocyte cell lines, IFN-gamma enzyme-linked immunospot (ELISPOT) assay with peripheral blood mononuclear cells, and 51Cr release cytotoxicity assay of rNcSRS2-stimulated effector cells. Four N. caninum-infected Holstein cattle developed NcSRS2 peptide-specific T lymphocytes detected ex vivo in peripheral blood by IFN-gamma ELISPOT and in vitro by measuring T-lymphocyte IFN-gamma production and cytotoxicity. An immunodominant region of NcSRS2 spanning amino acids 133 to 155 was recognized by CD4+ T lymphocytes from the four cattle. These findings support investigation of subunit N. caninum vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2 peptide-specific CTL and IFN-gamma-secreting T lymphocytes in cattle with varied MHC genotypes. 相似文献
54.
55.
56.
Special report. Steriod receptors in breast cancer. 总被引:5,自引:0,他引:5
E R DeSombre P P Carbone E V Jensen W L McGuire S A Wells J L Wittliff M B Lipsett 《The New England journal of medicine》1979,301(18):1011-1012
57.
Potential target sites in peripheral tissues for excitatory neurotransmission and excitotoxicity 总被引:7,自引:0,他引:7
Glutamate receptors (GluRs) are ubiquitously present in the central nervous system (CNS) as the major mediators of excitatory neurotransmission and excitotoxicity. Neural injury associated with trauma, stroke, epilepsy, and many neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's diseases and amyotrophic lateral sclerosis may be mediated by excessive activation of GluRs. Neurotoxicity associated with excitatory amino acids encountered in food, such as domoic acid and monosodium glutamate, has also been linked to GluRs. Less is known about GluRs outside the CNS. Recent observations suggest that several subtypes of GluRs are widely distributed in peripheral tissues. Using immunochemical and molecular techniques, the presence of GluR subtypes was demonstrated in the rat and monkey heart, with preferential distribution within the conducting system, nerve terminals, and cardiac ganglia. GluR subtypes NMDAR 1, GluR 2/3, and mGluR 2/3 are also present in kidney, liver, lung, spleen, and testis. Further investigations are needed to assess the role of these receptors in peripheral tissues and their importance in the toxicity of excitatory compounds. Therefore, food safety assessment and neurobiotechnology focusing on drugs designed to interact with GluRs should consider these tissues as potential target/effector sites. 相似文献
58.
C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro 总被引:1,自引:0,他引:1
We have previously shown that activated C1s complement and activated T
cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation
of desLys58 beta2m. This process can specifically be inhibited by
C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously
added desLys58 beta2m in nanomolar amounts to a one-way allogenic mixed
lymphocyte culture (MLC) increased the endogenous production of IL-2 and
the generation of allo-specific cytotoxic T lymphocytes. C1-inh was
purified from fresh human plasma and added to human or murine MLC and
mitogen-stimulated lymphocyte cultures grown in the presence of
complement-inactivated serum. Read-outs were cell proliferation, lymphokine
production and development of T cell-mediated cytotoxicity. We found that
addition of C1-inh to MLC and mitogen- exposed murine and human lymphocyte
cultures inhibited proliferation, the development of allospecific cytotoxic
activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12
and IFN-gamma. These data clearly demonstrate a regulatory function of
C1-inh on T cell- mediated immune functions.
相似文献
59.
The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry 总被引:8,自引:1,他引:8
Nistico L; Buzzetti R; Pritchard LE; Van der Auwera B; Giovannini C; Bosi E; Larrad MT; Rios MS; Chow CC; Cockram CS; Jacobs K; Mijovic C; Bain SC; Barnett AH; Vandewalle CL; Schuit F; Gorus FK; Tosi R; Pozzilli P; Todd JA 《Human molecular genetics》1996,5(7):1075-1080
Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus
is determined by a combination of environmental and genetic factors, which
include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin
gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2
cannot explain the clustering of type 1 diabetes in families, and a role
for other genes is inferred. In the present report we describe linkage and
association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte
associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong
candidate gene for T cell- mediated autoimmune disease because it encodes a
T cell receptor that mediates T cell apoptosis and is a vital negative
regulator of T cell activation. In addition, we provide supporting evidence
that CTLA-4 is associated with susceptibility to Graves' disease, another
organ- specific autoimmune disease.
相似文献
60.
Burwinkel B; Maichele AJ; Aagenaes O; Bakker HD; Lerner A; Shin YS; Strachan JA; Kilimann MW 《Human molecular genetics》1997,6(7):1109-1115
Glycogen storage disease due to phosphorylase kinase deficiency occurs in
several variants that differ in mode of inheritance and tissue-
specificity. This heterogeneity is suspected to be largely due to mutations
affecting different subunits and isoforms of phosphorylase kinase. The gene
of the ubiquitously expressed beta subunit, PHKB, was a candidate for
involvement in autosomally transmitted phosphorylase kinase deficiency of
liver and muscle. To identify such mutations, the complete PHKB coding
sequence was amplified by RT-PCR of RNA isolated from blood samples of
patients and analyzed by direct sequencing of PCR products. The
characterization of mutations was complemented by PCR of genomic DNA. In
one female and four male patients, we identified five independent nonsense
mutations (Y418ter; R428ter; Y974H+E975ter; Q656ter in two cases), one
single-base insertion in codon N421, one splice-site mutation affecting
exon 31, and a large deletion involving the loss of exon 8. Although these
severe translation-disrupting mutations occur in constitutively expressed
sequences of the only known beta subunit gene of phosphorylase kinase,
PHKB, they are associated with a surprisingly mild clinical phenotype,
affecting virtually only the liver, and relatively high residual enzyme
activity of approximately 10%.
相似文献