全文获取类型
收费全文 | 1475篇 |
免费 | 129篇 |
国内免费 | 72篇 |
专业分类
耳鼻咽喉 | 11篇 |
儿科学 | 19篇 |
妇产科学 | 32篇 |
基础医学 | 251篇 |
口腔科学 | 27篇 |
临床医学 | 122篇 |
内科学 | 295篇 |
皮肤病学 | 141篇 |
神经病学 | 36篇 |
特种医学 | 35篇 |
外科学 | 129篇 |
综合类 | 256篇 |
预防医学 | 61篇 |
眼科学 | 17篇 |
药学 | 112篇 |
中国医学 | 21篇 |
肿瘤学 | 111篇 |
出版年
2023年 | 7篇 |
2022年 | 16篇 |
2021年 | 27篇 |
2020年 | 25篇 |
2019年 | 12篇 |
2018年 | 19篇 |
2017年 | 25篇 |
2016年 | 55篇 |
2015年 | 44篇 |
2014年 | 91篇 |
2013年 | 83篇 |
2012年 | 110篇 |
2011年 | 126篇 |
2010年 | 114篇 |
2009年 | 114篇 |
2008年 | 103篇 |
2007年 | 107篇 |
2006年 | 96篇 |
2005年 | 89篇 |
2004年 | 64篇 |
2003年 | 43篇 |
2002年 | 30篇 |
2001年 | 27篇 |
2000年 | 22篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 15篇 |
1996年 | 19篇 |
1995年 | 24篇 |
1994年 | 13篇 |
1993年 | 8篇 |
1992年 | 11篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 13篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 12篇 |
1984年 | 8篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 3篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 8篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 3篇 |
排序方式: 共有1676条查询结果,搜索用时 31 毫秒
1.
Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour.
Anastasios Matzavinos Mark A J Chaplain Vladimir A Kuznetsov 《Mathematical medicine and biology》2004,21(1):1-34
In this paper a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. In particular, attention is focused upon the attack of tumour cells by so-called tumour-infiltrating cytotoxic lymphocytes (TICLs), in a small, multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. At this stage the immune cells and the tumour cells are considered to be in a state of dynamic equilibrium--cancer dormancy--a phenomenon which has been observed in primary tumours, micrometastases and residual disease after ablation of the primary tumour. Nonetheless, the precise biochemical and cellular mechanisms by which TICLs control cancer dormancy are still poorly understood from a biological and immunological point of view. Therefore we focus on the analysis of the spatio-temporal dynamics of tumour cells, immune cells and chemokines in an immunogenic tumour. The lymphocytes are assumed to migrate into the growing solid tumour and interact with the tumour cells in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation (sometimes even the death) of the lymphocytes. The migration of the TICLs is determined by a combination of random motility and chemotaxis in response to the presence of chemokines. The resulting system of four nonlinear partial differential equations (TICLs, tumour cells, complexes and chemokines) is analysed and numerical simulations are presented. We consider two different tumour geometries--multi-layered cell growth and multi-cellular spheroid growth. The numerical simulations demonstrate the existence of cell distributions that are quasi-stationary in time and heterogeneous in space. A linear stability analysis of the underlying (spatially homogeneous) ordinary differential equation (ODE) kinetics coupled with a numerical investigation of the ODE system reveals the existence of a stable limit cycle. This is verified further when a subsequent bifurcation analysis is undertaken using a numerical continuation package. These results then explain the complex heterogeneous spatio-temporal dynamics observed in the partial differential equation (PDE) system. Our approach may lead to a deeper understanding of the phenomenon of cancer dormancy and may be helpful in the future development of more effective anti-cancer vaccines. 相似文献
2.
目的:探讨支气管哮喘患者CD8+T细胞对单核/巨噬细胞抗原递呈功能的影响。方法:哮喘患者20例,健康对照22例,分别取静脉血5 mL,并分离MΦ、CD8+T细胞和B细胞。每份血样分成4组:MΦ递呈抗原组、CD8+T细胞参与MΦ递呈抗原组、CD8+T细胞体外活化后对MΦ递呈抗原影响组及自然状态下CD8+T细胞对MΦ细胞递呈抗原影响组。各组用CTLL2P抗原刺激18 h后,洗去刺激原,与自体B细胞共同孵育10 d,吸取上清液,测定特异性IgM、IgE、IgG含量。
结果:①哮喘患者MΦ单独递呈抗原,自体B细胞特异性IgM(A490值)(0.034±0.022)明显低于健康人(0.116±0.080)(P<0.05);CD8+T细胞与MΦ共同培养递呈抗原时,产生的特异性IgM(A490值)(0.031±0.021)低于健康人(0.079±0.064)(P<0.05);②哮喘患者CD8+T细胞与MΦ共同培养递呈抗原时,产生的特异性IgG(A490值)(0.102±0.041)明显高于健康人(0.081±0.067)(P<0.05),自然状态下及体外活化后CD8+T细胞与递呈抗原MΦ共同培养,产生的特异性IgG(A490值)(0.105±0.066, 0.079±0.059)与健康人(0.066±0.038, 0.069±0.047)无明显差别(P>0.05);③哮喘患者CD8+T细胞与MΦ共同培养递呈抗原产生的特异性IgE(A490值)(0.171±0.154)高于健康人(0.147±0.059)(P<0.05)。
结论:哮喘患者CD8+T细胞对MΦ递呈抗原产生免疫球蛋白有调节作用,而且参与哮喘发病。 相似文献
3.
目的:研究吗啡对不同淋巴细胞增殖的作用及纳洛酮的影响.方法:观察吗啡对未成熟的、静止的及活化的脾脏淋巴细胞体外增殖影响及纳洛酮的阻断作用.结果:吗啡(1×10~(-10)—1×10~(-6)mol L~(-1))能增加Con A诱导的T-细胞的增殖,1 μmol L~(-1)还能促进LPS诱导的B-细胞的增殖,同时这些增强作用都能被纳洛酮50μmol L~(-1)阻断,纳洛酮单独亦能促进活化T-细胞的增殖.而吗啡1×10~(-10)—1×10~(-5)mol L~(-1)对静止的脾脏淋巴细胞及Con A活化的胸腺淋巴细胞的增殖都无影响.但是吗啡1mmol L~(-1)能广泛抑制静止的、LPS活化的脾脏细胞及Con A活化的胸腺,脾脏淋巴细胞增殖,且都不能被纳洛酮阻断.结论:吗啡对活化T-和B-细胞的促进作用是由细胞表面的阿片受体介导的,此阿片受体随着淋巴细胞的成熟和活化而变化,而吗啡1 mmol L~(-1)对淋巴细胞增殖的抑制作用却不是由经典的阿片受体介导的. 相似文献
4.
单用达那唑(DNZ)治疗19例慢性再生障碍性贫血(CAA)病人。结果表明,基本治愈1例,缓解5例,明显进步7例,有效者共13例,总有效率为68.4%,初治者5/7例有效,有效率为71.4%;复治者8/12例有效,有效率为66.7%。治疗后与治疗前比较,血红蛋白、白细胞、血小板和网织红细胞均明显升高(P<0.001);骨髓红系、粒系及巨核细胞明显增高(P<0.05);T辅助细胞(CD4)明显增加、T抑制细胞(CD8)明显降低,CD4/CD8比值明显升高(P<0.05)。并结合文献对DNZ的作用原理进行讨论。 相似文献
5.
Ten patients with childhood optic neuritis (5 with a single attack of ON and 5 with later MS) were studied at various stages of the disease. Lymphocyte count and function were analysed in the peripheral blood of all patients, 3 repeatedly, and in one they were also analysed in the CSF. T-lymphocytes counts were normal in all but 2 MS cases who had high counts. In acute stages the T4/T8 ratio were high in 1/3 determinations, in recovery low in 2/2 determinations, and in stable stages normal in 6/8 determinations. Lymphocyte function, measured by PHA, ConA and PWM stimulation, was normal in all but one. One patient showed significantly higher T-cell percentages and a high number of stimulated lymphocytes in CSF but a lower count of suppressor cells than in the blood. We found no abnormalities specific to MS nor to childhood MS or to disease activity stage. Rather than peripheral blood, it would seem more worthwhile to study CSF to clarify the pathogenesis of ON and MS. 相似文献
6.
B细胞杂交瘤技术制备抗同种特异T细胞膜抗原单克隆抗体 总被引:1,自引:0,他引:1
目的:为进一步分析TCV免疫诱导同种免疫反应低下的机制。方法:采用B细胞杂交瘤技术获得分泌单克隆抗体的杂交瘤细胞。结果:两次的细胞融合中共得到12株稳定分泌单抗的杂交瘤细胞,为分析抗体在TCV中的作用提供条件。结论:TCV免疫可引起抗TCV细胞抗体的产生,以同系免疫的方法得到的活化B细胞用于B细胞杂交生产单抗是可行的。 相似文献
7.
目的研究大鼠肝移植后自发免疫耐受的形成与移植肝内CD4~ CD25~ 调节性T细胞(Tr细胞)的关系。方法按供、受者不同将实验分为3组。急性排斥组:DA大鼠为供者,LEW大鼠为受者;自发耐受组:LEW大鼠为供者,DA大鼠为受者;同基因组:供、受者均为DA大鼠。各组均建立大鼠原位肝移植模型。分别在肝移植术后4、7、14、30和90 d时采用密度梯度离心法分离移植肝内淋巴细胞,免疫磁珠分离(MACS)法分选出CD4~ CD25~ Tr细胞;用流式细胞术(FCM)检测细胞纯度,同时分析CD4~ CD25~ Tr细胞比例的变化;体外细胞增殖试验研究CD4~ CD25~ Tr细胞对CD4~ CD25~-T细胞的免疫抑制作用。结果肝移植早期,急性排斥组和自发耐受组移植肝内CD4~ CD25~ Tr细胞比例均明显增加,其中急性排斥组增加更为明显;移植后4 d左右,两组CD4~ CD25~ Tr细胞比例开始下降,急性排斥组的下降幅度较大;移植后30 d,自发耐受组受者的移植肝内CD4~ CD25~ Tr细胞比例达到第2次高峰,约在移植后90 d时下降至正常生理水平。移植后7 d左右,急性排斥组受者均因发生排斥反应而死亡,而自发耐受组受者均存活。此外,CD4~ CD25~ Tr细胞能有效抑制CD4~ CD25~-T细胞的增殖。结论CD4~ CD25~ Tr细胞是一种具有特异免疫调节功能的T细胞亚群,其主动的免疫抑制功能可能是诱导大鼠肝移植自发免疫耐受的机制之一。 相似文献
8.
Peripheral blood CD3 and CD4 T-lymphocyte reduction correlates with severity of liver cirrhosis 总被引:2,自引:0,他引:2
L. Lombardo A. Capaldi G. Poccardi P. Vineis 《International Journal of Clinical & Laboratory Research》1995,25(3):153-156
Summary Immunological disturbances with impairment of immune function and a higher incidence of lymphoproliferative disorders and
other malignancies have been described in liver cirrhosis patients. To investigate the pathogenetic mechanism(s) involved
in such associated we looked for a possible imbalance in peripheral blood T-lymphocyte subpopulations in patients with liver
cirrhosis of differing severity. Immunophenotyping and counts of peripheral blood T-lymphocyte subpopulations were carried
out using monoclonal antibodies conjugated with different fluorochromes in 31 consecutive cirrhotic patients and 23 matched
healthy volunteers. Univariate and multivariate analyses of lymphocyte phenotype counts were performed and odds ratios were
computed. Statistically significant associations, according to both univariate and multivariate analyses, were found between
case/control status and mean CD3 and CD4 T-lymphocyte counts (P<0.0001). A strong correlation was found between the Pugh’s index and CD3 and CD4 lymphocyte counts, with a clear reduction
of these phenotypes with increasing liver cirrhosis. Median CD3 and CD4 values were 2,283 and 1,329/μl respectively among
controls and 896, 801, and 492/μl and 515, 514, and 307/μl, respectively in categories A, B, and C of Pugh’s classification.
Very high odds ratios were found using the median values of CD3 and CD4 as a threshold. There was a statistically significant
decrease for each of the T-cell phenotypes studied (CD2, CD3, CD4, CD8, CD16, CD19, CD20, CD56, CD57) between patients and
controls (P<0.0001). The progressive and severity-related decrease in mean peripheral blood CD3 and CD4 counts in liver cirrhosis suggests
a progressive impairment of protective immune function and may be a factor facilitating malignancy in cirrhotic patients. 相似文献
9.
目的: 通过对小鼠派氏集合淋巴结(PPs)、肠系膜淋巴结(MLNs)和腹股沟淋巴结(ILNs)的比较性研究,以分析PPs T细胞活化和调节性T细胞的功能特点。 方法: 无菌分离小鼠PPs、MLNs和ILNs,分别制备单个淋巴细胞悬液,运用流式细胞术结合荧光抗体染色技术来检测CD3+T细胞、CD3+CD4+辅助性T细胞和CD4+CD25+调节性T细胞的比例;用多克隆刺激剂刀豆蛋白A(Con A)、佛波醇酯(PDB)和离子霉素(Ion) 刺激活化淋巴细胞,随后运用流式细胞术结合双色荧光抗体染色技术来检测T细胞早期活化标志CD69的表达水平。 结果: PPs内CD3+T细胞所占比例明显低于MLNs和ILNs,然而CD4+CD25+调节性T细胞的比例明显高于MLNs和ILNs;在没有加入刺激剂的培养条件下,PPs来源的T细胞CD69的表达水平明显高于MLNs和ILNs来源的T细胞,MLNs来源的T细胞CD69的表达水平明显高于ILNs来源的T细胞;而在加入Con A或者单纯PDB的培养条件下,PPs来源的T细胞却表现出低反应性;在加入PDB+Ion的培养条件下,3者来源的T细胞CD69的表达水平没有明显差别。 结论: PPs内CD3+T细胞所占比例较低,CD4+CD25+调节性T细胞的比例较高,这可能是PPs整体T细胞低反应性的原因之一;PPs来源T细胞的高基础活化率可能与其不断接触小肠来源的食物和共生菌抗原有关;PPs来源T细胞选择性地对某些刺激剂表现出低反应性,提示这群细胞处于某种程度的无能状态。上述特征的生物学意义在于避免因为不断接受小肠来源的食物和共生菌抗原的刺激而发生病理性炎症的同时还保留对病原微生物抗原的应答。 相似文献
10.
目的:观察异体角膜体外对人外周血T细胞及其亚群CD25分子表达的影响。方法: 异体角膜与外周血淋巴细胞体外共同培养后,进行单克隆抗体标记和流式细胞分析。结果: 对照组T细胞CD25表达为25.2%;受角膜或沸波醇酯(PDB)激活后T细胞CD25表达分别为56.8%和80.9%;受角膜和沸波醇酯共同激活后T细胞CD25表达为70.2%;受异体角膜激活后,CD4和CD8 T淋巴细胞CD25表达分别为67.3%和52.3%。结论: 异体角膜组织体外能够刺激人外周T细胞CD25表达和T细胞活化,CD4 T细胞比CD8 T细胞活化更明显。 相似文献