全文获取类型
收费全文 | 54386篇 |
免费 | 2599篇 |
国内免费 | 4463篇 |
专业分类
耳鼻咽喉 | 508篇 |
儿科学 | 718篇 |
妇产科学 | 1015篇 |
基础医学 | 8967篇 |
口腔科学 | 770篇 |
临床医学 | 3386篇 |
内科学 | 10355篇 |
皮肤病学 | 490篇 |
神经病学 | 3609篇 |
特种医学 | 1031篇 |
外国民族医学 | 8篇 |
外科学 | 5266篇 |
综合类 | 6350篇 |
现状与发展 | 74篇 |
一般理论 | 20篇 |
预防医学 | 2606篇 |
眼科学 | 2193篇 |
药学 | 6137篇 |
8篇 | |
中国医学 | 1356篇 |
肿瘤学 | 6581篇 |
出版年
2024年 | 133篇 |
2023年 | 552篇 |
2022年 | 392篇 |
2021年 | 295篇 |
2020年 | 220篇 |
2019年 | 183篇 |
2018年 | 183篇 |
2017年 | 93篇 |
2016年 | 155篇 |
2015年 | 261篇 |
2014年 | 633篇 |
2013年 | 292篇 |
2012年 | 9783篇 |
2011年 | 10757篇 |
2010年 | 1913篇 |
2009年 | 735篇 |
2008年 | 5598篇 |
2007年 | 5682篇 |
2006年 | 4990篇 |
2005年 | 4501篇 |
2004年 | 3594篇 |
2003年 | 2995篇 |
2002年 | 2417篇 |
2001年 | 1260篇 |
2000年 | 1716篇 |
1999年 | 916篇 |
1998年 | 415篇 |
1997年 | 113篇 |
1996年 | 66篇 |
1995年 | 78篇 |
1994年 | 44篇 |
1993年 | 29篇 |
1992年 | 13篇 |
1991年 | 16篇 |
1990年 | 12篇 |
1989年 | 48篇 |
1988年 | 47篇 |
1987年 | 65篇 |
1986年 | 21篇 |
1985年 | 44篇 |
1984年 | 48篇 |
1983年 | 45篇 |
1982年 | 21篇 |
1981年 | 24篇 |
1980年 | 25篇 |
1979年 | 18篇 |
1978年 | 1篇 |
1975年 | 3篇 |
1964年 | 2篇 |
1959年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
Committing embryonic stem cells to early endocrine pancreas in vitro 总被引:12,自引:0,他引:12
Ku HT Zhang N Kubo A O'Connor R Mao M Keller G Bromberg JS 《Stem cells (Dayton, Ohio)》2004,22(7):1205-1217
A panel of genetic markers was used to assess the in vitro commitment of murine embryonic stem (ES) cells toward the endoderm-derived pancreas and to distinguish insulin-expressing cells of this lineage from other lineages such as neuron, liver, and yolk sac. There are two nonallelic insulin genes in mice. Neuronal cells express only insulin II, whereas the pancreas expresses both insulin I and II. Yolk sac and fetal liver express predominately insulin II, small amounts of insulin I, and no glucagon. We found that ES-derived embryoid bodies cultured in the presence of stage-specific concentrations of monothio-glycerol and 15% fetal calf serum, followed by serum-free conditions, give rise to a population that expresses insulin I, insulin II, pdx-1 (a pancreas marker), and Sox17 (an endoderm marker). Immunohistochemical staining shows intracellular insulin particles, and its de novo production was confirmed by staining for C-peptide. Most, but not all, of the insulin+ or C-peptide+ cells coexpress glucagon, demonstrating a differentiation pathway to pancreas rather than yolk sac or fetal liver. Addition of beta-cell specification and differentiation factors activin beta B, nicotinamide, and exendin-4 to later-stage culture increased insulin-positive cells to 2.73% of the total population, compared with the control culture, which gave rise to less than 1% insulin-staining cells. These findings suggest that stepwise culture manipulations can direct ES cells to become early endocrine pancreas. 相似文献
52.
53.
BACKGROUND: Prostate-specific membrane antigen (PSMA) is a well characterized prostate-specific tumor associated antigen. Its expression is elevated in prostate carcinoma, particularly in metastatic and recurrent lesions. These observations suggest that PSMA can be used as immune target to induce tumor cell-specific recognition by the host and, consequently tumor rejection. We utilized a DNA-based vaccine to specifically enhance PSMA expression. An immune modulator, such as CpG oligodeoxynucleotides which promote Th1-type immune responses was combined to increase the efficacy of tumor recognition and elimination. METHODS: A eukaryotic expression plasmid pCDNA3.1-PSMA encoding full-length PSMA was constructed. C57BL/6 mice were immunized with endotoxin-free pCDNA3.1-PSMA alone or in combination with CpG oligodeoxynucleotides by intramuscular injection. After 4 immunizations, PSMA specific antibodies and cytotoxic T lymphocyte reactivity were measured. Immunized C57BL/6 mice were also challenged subcutaneously with B16 cells transfected with PSMA to evaluate suppression of tumor growth. RESULTS: Vaccine-specific cytotoxic T lymphocytes reactive with B16 cells expressing PSMA could be induced with this treatment schedule. Immune protection was observed in vaccinated mice as indicated by increased tumor growth in the control group (100%) compared with the groups vaccinated with DNA alone (66.7%) or DNA plus CpG oligodeoxynucleotides (50%) respectively. Average tumor volume was smaller in vaccinated groups and tumor-free survival time was prolonged by the vaccination. CONCLUSION: The current findings suggest that specific anti-tumor immune response can be induced by DNA vaccines expressing PSMA. In addition, the suppression of in vivo growth of tumor cells expressing PSMA was augmented by CpG oligodeoxynucleotides. This strategy may provide a new venue for the treatment of carcinoma of prostate after failure of standard therapy. 相似文献
54.
55.
56.
57.
58.
干扰素调节因子-7对肿瘤细胞生长的影响 总被引:1,自引:0,他引:1
干扰素 (IFN)调节因子 (IFNregulatoryfactor ,IRF)是一组通过与IFN基因中顺式元件结合来调节IFN及其诱导性基因表达的核因子。到目前为止 ,已发现至少有 9种IRF ,以IRF 1和IRF 2的研究最多。基本明确IRF 1是免疫上调因子 ,促进IFN γ表达 ;IRF 2是免疫负反馈调节因子 ,抑制IRF 1的过度表达。近年发现 ,IRF 1直接抑制肿瘤生长 ,上调MHCⅠ和MHCⅡ的表达。IRF 3也是肿瘤细胞生长的强抑制因子 ,诱发肿瘤细胞凋亡。IRF 7是 1998年发现的另一IRF因子 ,与IRF 3在氨基酸… 相似文献
59.
Piglets infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV) are born severely immunocompromised. In this article we more closely examine the effects of in utero PRRSV infection on circulating and thymic T cell populations. Numbers of CD4+, CD8+, and dual-positive lymphocytes were quantitated in circulation and in the thymus during the 2 weeks following birth. At birth we found that the number of circulating lymphocytes was suppressed by 60%. Lymphocyte numbers were also suppressed by 42% at day 7, but by day 14 the number of lymphocytes had rebounded and was actually 47% greater than controls. At birth and day 7, a drop in the number of CD4+ cells could partially explain the suppression we observed, while the rebound in total lymphocyte numbers seen at day 14 was due to a nearly fourfold increase in the number of circulating CD8+ cells. As a result, the normal CD4+:CD8+ ratio of between 1.4 and 2.2 for neonatal pigs was reduced to 0.1-0.5. The thymuses of infected piglets were found to be 50% smaller than those of control pigs and were characterized by cortical involution and severe cortical depletion of thymocytes. Analysis of the population of thymocytes revealed that double-positive thymocytes were suppressed to a greater degree than either single positive subpopulation. In addition, we show that the number of thymocytes undergoing apoptosis was increased twofold in piglets infected with PRRSV. Taken together, these results help explain the dramatic immunosuppression observed in neonatal animals infected in utero with PRRSV. 相似文献
60.
Genomic analysis of the nuclear receptor family: new insights into structure, regulation, and evolution from the rat genome
下载免费PDF全文
![点击此处可从《Genome research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Zhang Z Burch PE Cooney AJ Lanz RB Pereira FA Wu J Gibbs RA Weinstock G Wheeler DA 《Genome research》2004,14(4):580-590
Completion of the Rattus norvegicus genome sequence enabled a global inventory and analysis of the nuclear receptors (NRs) in three mammalian species. Forty-nine NR members were found in mouse, 48 in human. Forty-seven were found in the rat, with gaps at the locations expected for the other two. Pairwise comparisons of their distribution in rat, mouse, and human identified 11 syntenic NR gene blocks, including three small clusters of two or three closely related genes, each spanning 40 kb to 1700 kb. The exon structure of the ligand-binding domain suggests that exon shuffling has played a role in the evolution of this family. An invariant splice junction in all members of the NR family except LXRbeta suggests a functional role for the intron. The ligand-binding domains of PXR and CAR are among the most divergent in the family. Their higher nucleotide substitution rates may be related to the central role played by these two NRs in the metabolism of the foreign compounds and may have resulted from limited positive selection. 相似文献