全文获取类型
收费全文 | 125396篇 |
免费 | 11044篇 |
国内免费 | 5779篇 |
专业分类
耳鼻咽喉 | 897篇 |
儿科学 | 4302篇 |
妇产科学 | 3033篇 |
基础医学 | 15619篇 |
口腔科学 | 3171篇 |
临床医学 | 11582篇 |
内科学 | 19917篇 |
皮肤病学 | 1861篇 |
神经病学 | 9768篇 |
特种医学 | 2364篇 |
外国民族医学 | 37篇 |
外科学 | 10277篇 |
综合类 | 19910篇 |
现状与发展 | 20篇 |
预防医学 | 9608篇 |
眼科学 | 3339篇 |
药学 | 12144篇 |
37篇 | |
中国医学 | 4294篇 |
肿瘤学 | 10039篇 |
出版年
2024年 | 190篇 |
2023年 | 1404篇 |
2022年 | 2540篇 |
2021年 | 4249篇 |
2020年 | 3811篇 |
2019年 | 3545篇 |
2018年 | 3463篇 |
2017年 | 4013篇 |
2016年 | 4292篇 |
2015年 | 4350篇 |
2014年 | 7570篇 |
2013年 | 8851篇 |
2012年 | 7677篇 |
2011年 | 8604篇 |
2010年 | 7139篇 |
2009年 | 6795篇 |
2008年 | 7050篇 |
2007年 | 7101篇 |
2006年 | 6393篇 |
2005年 | 5801篇 |
2004年 | 4975篇 |
2003年 | 4322篇 |
2002年 | 3528篇 |
2001年 | 3139篇 |
2000年 | 2652篇 |
1999年 | 2265篇 |
1998年 | 1946篇 |
1997年 | 1738篇 |
1996年 | 1622篇 |
1995年 | 1525篇 |
1994年 | 1296篇 |
1993年 | 1083篇 |
1992年 | 968篇 |
1991年 | 811篇 |
1990年 | 741篇 |
1989年 | 588篇 |
1988年 | 467篇 |
1987年 | 423篇 |
1986年 | 366篇 |
1985年 | 520篇 |
1984年 | 412篇 |
1983年 | 269篇 |
1982年 | 380篇 |
1981年 | 254篇 |
1980年 | 234篇 |
1979年 | 162篇 |
1978年 | 152篇 |
1977年 | 117篇 |
1976年 | 117篇 |
1975年 | 70篇 |
排序方式: 共有10000条查询结果,搜索用时 323 毫秒
991.
NGF在成年猴脑的分布 总被引:1,自引:1,他引:1
为了解NGF在成年猴脑的分布,采用免疫组化SP法对成年猴脑多个冠状位切片进行免疫组化反应。结果证明,NGF阳性反应神经元主要分布于大脑皮质Ⅲ、V层,小脑Purkinje细胞,海马,齿状回,纹状体,脑干网状结构等处。此外,在黑质、舌下神经核、迷走神经背核、前庭神经核、三叉神经核、疑核、下橄榄核也出现NGF阳性反应。在大脑和脑干还观察到NGF阳性胶质细胞。本实验结果表明,在成年猴脑的多个脑区有NGF表达,提示NGF可能涉及猴脑某些神经元及胶质细胞的生理过程。 相似文献
992.
目的:用体外实验观察多种因素(包括亚砷酸钠、TNF-α、IL-6及烧伤血清、创伤血清)对中性白细胞(PMN)凋亡的影响,为探索一种新的保护组织免遭继发性损害的方法提供依据。方法:分离纯化人外周血PMN,与亚砷酸钠(Ars)、TNF-α、IL-6及烧伤血清、创伤血清作用后,测定凋亡比例、CD 11 b表达、呼吸爆发、胞质Ca2+浓度的改变。结果:Ars浓度与PMN凋亡呈剂量依赖关系,激活的PMN却对Ars失敏;IL-6使PMN凋亡延迟(与24 h对照相比,P<0.05),抑制CD 11 b表达(与24 h对照相比,P<0.01);烧伤血清和创伤血清的作用较IL-6更为明显。结论:发现PMN激活后对Ars失敏,其机理不清;CD 11 b表达升高与PMN凋亡增多呈正相关;IL-6、烧伤血清、创伤血清能延迟PMN凋亡,部分恢复PMN的功能。 相似文献
993.
Shinohara Y Iwasaki H Ota N Nakajima T Kodaira M Kajita M Shiba T Emi M 《Journal of human genetics》2001,46(1):50-51
The nuclear factor kappa-B 2 (NFKB2) gene is a member of the NFKB/Rel gene family, which is known to be a pivotal regulator of the acute phase of the inflammatory
response and of immune responses. We identified three novel single nucleotide polymorphisms (SNPs) and determined their allelic
frequencies, as determined by the sequencing of 48 alleles of the entire gene in a Japanese population sample. Two of the
three polymorphisms were identified at nucleotide (nt) position 1837 (T/C) and nt position, 1867 (GG/G) in the upstream region
of the gene. The other polymorphism was identified at nt position 2584 (G/T) within intron 1. These polymorphisms will be
useful in genetic studies of the processes involved in inflammatory responses and in bone differentiation.
Received: October 17, 2000 / Accepted: October 23, 2000 相似文献
994.
胸腹水组织因子及组织因子途径抑制物的检测及其意义 总被引:2,自引:0,他引:2
目的研究三组疾病胸腹水组织因子(Tissue factor,TF)及组织因子途径抑制物(Tissue factor pathway inhibitor,TFPI)的表达及其鉴别诊断意义。方法TF和TFPI采用ELISA法测定抗原表达。结果胸腹水TF水平和TFPI水平,恶性肿瘤组(570.04±627.53)ng/L,(28.60±15.57)μg/L和结核病组(283.82±143.16)ng/L,(31.16±12.26)μg/L明显高于肝硬化组(60.83±66.87)ng/L,(7.84±5.45)μg/L,P<0.01。TF/TFPI比值则为恶性肿瘤组(32.17±44.19)明显高于结核病组(13.55±13.15)和肝硬化组(11.22±9.05,P<0.05)。在恶性肿瘤组中,胸腹水癌细胞阳性组的TF表达(1106.92±1244.28)ng/L高于阴性组(331.08±295.84)ng/L,P<0.05。而阳性组的TFPI水平(27.35±17.75)μg/L与阴性组(30.34±13.20)μg/L无明显差异(P>0.05)。TF/TFPI比值则为阳性组(59.59±65.10)明显高于阴性组(11.54±8.37,P<0.01)。结论检测胸腹水TF和TFPI并分析TF/TFPI比值可以作为临床实验室有鉴别诊断意义的辅助指标,同时还可了解疾病的某些病理机制,尤其是肿瘤的某些生物学行为。 相似文献
995.
Genetics of congenital hyperinsulinism 总被引:4,自引:0,他引:4
Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous entity and causes severe hypoglycemia in neonates
and infants. The clinical heterogeneity is manifested by severity ranging from extremely severe, life-threatening disease
to very mild clinical symptoms, which may even be difficult to identify. Furthermore, clinical responsiveness to medical and
surgical management is extremely variable.
Recent discoveries have begun to clarify the molecular etiology of this disease in about 50% of cases. Mutations in five different
genes have been identified in patients with this clinical syndrome. Most cases are caused by mutations in the genes ABCC8 and KCNJ11 coding for either of the two subunits of the beta-cell KATP channel (SUR1 and Kir6.2). Recessive mutations of the beta-cell
K(ATP) channel genes cause diffuse HI, whereas loss of heterozygosity together with inheritance of a paternal mutation causes
focal adenomatous HI. In other cases, CHI is caused by mutations in genes coding for the beta-cell enzymes glucokinase (GK),
glutamate dehydrogenase (GDH), and SCHAD.
However, for as many as 50% of the cases, no genetic etiology has yet been determined. The study of the genetics of this disease
has provided important new information regarding beta-cell physiology. 相似文献
996.
997.
Specific cytotoxic T lymphocytes in gene therapy 总被引:1,自引:0,他引:1
U. Altenschmidt Dirk Moritz B. Groner 《Journal of molecular medicine (Berlin, Germany)》1997,75(4):259-266
Cytotoxic T lymphocytes possess the capacity to lyse target cells which express antigens on their surface recognized by the
T cell receptor. These cells are crucial in the body’s defense against foreign antigens. It has long been a goal of tumor
biology to utilize T cells, specialized in the elimination of unwanted cells, for the treatment of cancer. The killing activity
of T lymphocytes is restricted to specific antigen-presenting cells. For this reason the use of cytotoxic T cells in the elimination
of cancer cells is limited to cancer cells which present neoantigens on their surface. To circumvent this limitation we describe
a procedure in which the ζ component of the T cell receptor is genetically manipulated and equipped with an extracellular
recognition domain. Introduction of a chimeric gene, consisting of the ζ chain of the T cell receptor and a single-chain antibody
domain, into cytotoxic T lymphocytes results in T cells with a predetermined recognition specificity for particular tumor
cells. The MHC restriction of target cell recognition can be avoided and tumor cells recognized by the single chain antibody
domain can be recognized and lysed. Retroviral-mediated gene transduction was used to introduce chimeric ζ chain constructs
into primary T cells of mice. The cocultivation of retrovirus producing helper cells with in vitro activated T lymphocytes
led to a high gene transduction efficiency into primary T cells. These primary T cells assumed a predetermined specificity
for target cell recognition and lysis. The production and provision of tumor cell specific T lymphocytes might not be sufficient
to eradicate large tumors in vivo. Using a Schwannoma cell line, we showed that transplanted tumors secrete transforming growth
factor β and thereby stifle the action of lymphocytes. We suggest that a coordinated strategy including the suppression of
tumor cells specific antilymphocyte action and the provision of tumor cell specific T cells might be required to successfully
eliminate tumor cells in vivo.
Received: 13 September 1996 / Accepted: 30 October 1996 相似文献
998.
目的:探讨单发性和多发性浅表膀胱移行细胞癌组织中血管内皮生长因子(VEGF)的表达及意义。方法:采用免疫组化方法对60例浅表膀胱移行细胞癌组织及10例正常膀胱组织进行血管内皮生长因子(VEGF)的检测,观察单发性和多发性浅表膀胱移行细胞癌组织中VEGF表达的关系。结果:多发性浅表膀胱移行细胞癌VEGF的高表达明显高于单发者的高表达;VEGF高表达的浅表膀胱移行细胞癌的患者的复发率明显高于低表达者的复发率。结论:VEGF表达的高低与浅表膀胱移行细胞癌的生物学行为有关。 相似文献
999.
目的:探讨抗巨噬细胞移动抑制因子单克隆抗体(anti-MIFMAb)在油酸诱导的大鼠急性肺损伤(ALI)中的干预作用,及其对巨噬细胞移动抑制因子(MIF)和细胞间粘附分子-1(ICAM-1)表达的影响。方法:雄性Wistar大鼠静脉注射油酸复制ALI为油酸组,静脉注射生理盐水为对照组,大鼠先给予抗-MIF单抗腹腔注射后再给予油酸静脉注射为抗-MIF单抗干预组。静注后4h,3组大鼠分别测定动脉血氧分压(PaO2),肺泡通透指数等肺损伤指标;用ELISA法测定支气管肺泡灌洗液(BALF)中可溶性细胞间粘附分子-1(sICAM-1)水平;用原位杂交检测MIF和ICAM-1mRNA表达水平;用免疫组化双重套染方法检测巨噬细胞浸润程度与MIF表达的关系。结果:油酸组PaO2低于对照组和干预组,肺通透性指数高于对照组和干预组(P<0.01),BALF中sICAM-1水平显著高于对照组和干预组(P<0.01)。油酸组肺组织MIF和ICAM-1表达明显高于对照组和干预组(P<0.01),经抗-MIF单抗干预ICAM-1表达变化不明显,但MIF表达显著下调,巨噬细胞浸润减少且肺损伤指标改善。结论:MIF和ICAM-1在介导巨噬细胞对组织的粘附、浸润和ALI的发生发展中起重要作用,抗-MIF单抗主要通过阻断MIF表达,减少巨噬细胞浸润而起肺保护作用。 相似文献
1000.
van Esch WJ Reparon-Schuijt CC Hamstra HJ van Kooten C Logtenberg T Breedveld FC Verweij CL 《Journal of autoimmunity》2002,19(4):241-250
Recent data indicate that rheumatoid factors (RFs) that occur in patients with rheumatoid arthritis (RA) are derived from Ig-producing terminally differentiated CD20-, CD38+ plasma cells present in synovial fluids (SFs). Phage antibody display libraries were constructed using CD38+ plasma cells isolated from SFs of two RF-seropositive RA patients. The libraries were enriched for phage antibodies (Phabs) binding to human IgG (HuIgG) Fc fragments and the sequences of their V genes were analysed. These data provided further evidence for an Ag-driven immune response in patients with RA, including expansion of clonally related B cells, selection and isotype switching, all hallmarks of a germinal center reaction. In the present study, the functional characteristics of these HuIgG Fc-binding monoclonal (mo) Phabs were further analysed in order to provide more insight into the specificity of HuIgG Fc-binding Phabs. Remarkably, all HuIgG Fc-binding moPhabs tested (n=48; derived from four different libraries) displayed polyreactivity. Structural analysis of the CDR3 regions revealed characteristic features of polyreactive Igs. Most H chain CDR3 regions harboured tryptophan/tyrosine-rich parts and approximately 60% of the L chain CDR3 regions of both RA patients displayed an identical stretch of amino acids (W/Y-D-S-S). Supportive for a dominant role of VH in specificity, exchange of VL regions with a single VH region yielded moPhabs with similar specificities. All together, the data suggest the presence of an Ag-driven process in the joints of patients with RA, including somatic mutation and clonal selection entailing isotype switching, resulting in the differentiation of B cells into polyreactive RF-secreting plasma cells. 相似文献