全文获取类型
收费全文 | 52130篇 |
免费 | 4225篇 |
国内免费 | 123篇 |
专业分类
耳鼻咽喉 | 420篇 |
儿科学 | 2021篇 |
妇产科学 | 1349篇 |
基础医学 | 7420篇 |
口腔科学 | 1119篇 |
临床医学 | 7192篇 |
内科学 | 10213篇 |
皮肤病学 | 939篇 |
神经病学 | 5309篇 |
特种医学 | 1194篇 |
外科学 | 4826篇 |
综合类 | 541篇 |
一般理论 | 64篇 |
预防医学 | 6180篇 |
眼科学 | 723篇 |
药学 | 2936篇 |
2篇 | |
中国医学 | 58篇 |
肿瘤学 | 3972篇 |
出版年
2024年 | 67篇 |
2023年 | 444篇 |
2022年 | 615篇 |
2021年 | 1352篇 |
2020年 | 991篇 |
2019年 | 1486篇 |
2018年 | 1611篇 |
2017年 | 1276篇 |
2016年 | 1420篇 |
2015年 | 1487篇 |
2014年 | 1896篇 |
2013年 | 2780篇 |
2012年 | 3913篇 |
2011年 | 4031篇 |
2010年 | 2214篇 |
2009年 | 1945篇 |
2008年 | 3279篇 |
2007年 | 3396篇 |
2006年 | 3298篇 |
2005年 | 3104篇 |
2004年 | 3027篇 |
2003年 | 2787篇 |
2002年 | 2497篇 |
2001年 | 539篇 |
2000年 | 427篇 |
1999年 | 485篇 |
1998年 | 590篇 |
1997年 | 455篇 |
1996年 | 390篇 |
1995年 | 392篇 |
1994年 | 306篇 |
1993年 | 301篇 |
1992年 | 289篇 |
1991年 | 252篇 |
1990年 | 254篇 |
1989年 | 237篇 |
1988年 | 227篇 |
1987年 | 175篇 |
1986年 | 172篇 |
1985年 | 198篇 |
1984年 | 173篇 |
1983年 | 158篇 |
1982年 | 171篇 |
1981年 | 164篇 |
1980年 | 135篇 |
1979年 | 117篇 |
1978年 | 107篇 |
1977年 | 76篇 |
1973年 | 81篇 |
1972年 | 65篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
91.
Anne M Lewis Sheelu Varghese Hui Xu H Richard Alexander 《Journal of translational medicine》2006,4(1):48
The tumor microenvironment consists of tumor, immune, stromal, and inflammatory cells which produce cytokines, growth factors,
and adhesion molecules that promote tumor progression and metastasis. Of particular interest in this setting is interleukin-1
(IL-1), a pleiotropic cytokine with numerous roles in both physiological and pathological states. It is known to be up regulated
in many tumor types and has been implicated as a factor in tumor progression via the expression of metastatic and angiogenic
genes and growth factors. A number of studies have reported that high IL-1 concentrations within the tumor microenvironment
are associated with a more virulent tumor phenotype. Solid tumors in which IL-1 has been shown to be up regulated include
breast, colon, lung, head and neck cancers, and melanomas, and patients with IL-1 producing tumors have generally bad prognoses.
The exact mechanisms by which IL-1 promotes tumor growth remain unclear, though the protein is believed to act via induction
of pro-metastatic genes such as matrix metalloproteinases and through the stimulation of adjacent cells to produce angiogenic
proteins and growth factors such as VEGF, IL-8, IL-6, TNFα, and TGFβ. The IL-1 receptor antagonist (IL-1ra) is a naturally
occurring inhibitor to IL-1 and acts by binding to the IL-1 receptor without activating it. The protein has been shown to
decrease tumor growth, angiogenesis, and metastases in murine xenograft models. Our focus in this review is to summarize the
known data on the role of IL-1 in tumor progression and metastasis and the use of IL-1 inhibition as a novel therapeutic approach
in the treatment of solid organ malignancies. 相似文献
92.
93.
94.
95.
Cocaine's enhancement of dopaminergic neurotransmission in the mesolimbic pathway plays a critical role in the initial reinforcing properties of this drug. However, other neurotransmitter systems are also integral to the addiction process. A large body of data indicates that opioids and dopamine together mediate emotional and reinforced behaviors. In support of this, cocaine-mediated increases in activation of dopamine D1 receptors (D1R) results in a desensitization of δ-opioid receptor (DOR) signaling through adenylyl cyclase (AC) in striatal neurons. To further define cellular mechanisms underlying this effect, the subcellular distribution of DOR and D1R was examined in the rat dorsolateral striatum. Dual immunoperoxidase/gold-silver detection combined with electron microscopy was used to identify DOR and D1R immunoreactivities in the same section of tissue. Semi-quantitative analysis revealed that a subset of dendritic cellular profiles exhibited both DOR and D1R immunoreactivities. Of 198 randomly sampled D1R immunoreactive profiles, 43% contained DOR. Similarly of 165 DOR-labeled cellular profiles, 52% contained D1R. The present data provide ultrastructural evidence for co-existence between DOR and D1R in striatal neurons, suggesting a possible mechanism whereby D1R modulation may alter DOR function. 相似文献
96.
Jean-Fran?ois Ghersi-Egea Nathalie Strazielle Audrey Murat Anne Jouvet Annie Buénerd Marie-Fran?oise Belin 《Journal of cerebral blood flow and metabolism》2006,26(9):1165-1175
The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells. 相似文献
97.
98.
99.
100.