全文获取类型
收费全文 | 691篇 |
免费 | 72篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 13篇 |
妇产科学 | 4篇 |
基础医学 | 75篇 |
口腔科学 | 19篇 |
临床医学 | 61篇 |
内科学 | 225篇 |
皮肤病学 | 9篇 |
神经病学 | 117篇 |
特种医学 | 12篇 |
外科学 | 69篇 |
综合类 | 5篇 |
预防医学 | 27篇 |
眼科学 | 11篇 |
药学 | 38篇 |
中国医学 | 1篇 |
肿瘤学 | 79篇 |
出版年
2023年 | 12篇 |
2022年 | 12篇 |
2021年 | 49篇 |
2020年 | 25篇 |
2019年 | 30篇 |
2018年 | 35篇 |
2017年 | 24篇 |
2016年 | 24篇 |
2015年 | 32篇 |
2014年 | 24篇 |
2013年 | 33篇 |
2012年 | 42篇 |
2011年 | 59篇 |
2010年 | 18篇 |
2009年 | 17篇 |
2008年 | 31篇 |
2007年 | 17篇 |
2006年 | 30篇 |
2005年 | 22篇 |
2004年 | 17篇 |
2003年 | 30篇 |
2002年 | 30篇 |
2001年 | 21篇 |
2000年 | 19篇 |
1999年 | 22篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 8篇 |
1995年 | 6篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 9篇 |
1988年 | 6篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1979年 | 2篇 |
排序方式: 共有766条查询结果,搜索用时 15 毫秒
1.
2.
Namiki T Yanagawa S Izumo T Ishikawa M Tachibana M Kawakami Y Yokozeki H Nishioka K Kaneko Y 《Cancer Genetics and Cytogenetics》2005,157(1):1-11
To clarify the correlation of genomic alterations with clinical and histological features, we performed metaphase comparative genomic hybridization analysis on 20 primary cutaneous melanomas, which were obtained by laser capture or manual microdissection, and 16 melanoma cell lines. There were no differences in the average number of aberrations between acral melanomas (AM) and non-AM, although gains of 5q and 11q13 were more frequent (P=0.05) and 10q loss was less frequent (P=0.01) in AM than in non-AM. Although tumor thickness is considered a measurable estimate of clinical expression, there were no differences in the average number of aberrations among 4 groups, classified by thickness of the tumor. While the majority of aberrations were equally distributed among the 4 groups, 6p gains were found only in the thickest tumors. Patients with 6p or 1q gains had a lower overall survival rate than those without them (P=0.0002 or P=0.013). While gains of 1q, 2q, 3p, 3q, 7q, 20p, and 20q were more frequent in the cell lines than in the primary tumors (P<0.01), losses of 6q, 9p, 10p, and 10q were equally found in both cell lines and primary tumors. The present study showed that chromosomal aberrations had already occurred in the thinner tumors, and that 6p and 1q gains may be a prognostic factor. 相似文献
3.
Nishida Hayato Fukuhara Hiroki Nawano Takaaki Kanno Hidenori Yagi Mayu Yamagishi Atsushi Sakurai Toshihiko Naito Sei Kato Tomoyuki Kudo Kosuke Ichikawa Kazunobu Tsuchiya Norihiko 《Clinical and experimental nephrology》2021,25(12):1346-1353
Clinical and Experimental Nephrology - Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable... 相似文献
4.
Marked Suppression of T Cells by a Benzothiophene
Derivative in Patients with Human T-Lymphotropic Virus Type
I-Associated Myelopathy/Tropical Spastic Paraparesis
下载免费PDF全文
![点击此处可从《Clinical and Vaccine Immunology : CVI》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Masahiko Makino Miyuki Azuma Shin-Ichi Wakamatsu Yukio Suruga Shuji Izumo Mitchel M. Yokoyama Masanori Baba 《Clinical and Vaccine Immunology : CVI》1999,6(3):316-322
In a search for new anti-autoimmune agents that selectively
suppress activation of autoreactive T cells, one such agent,
5-methyl-3-(1-methylethoxy)benzo[b]thiophene-2-carboxamide
(CI-959-A), was found to be effective. This compound, which is known to
suppress tumor necrosis factor alpha (TNF-α)-induced CD54 expression,
inhibited the primary proliferative response of the T cell to antigen
(Ag)-presenting cells (APCs) including allogenic dendritic cells (DCs),
autologous Epstein-Barr virus-infected B cells, and human T
lymphotropic virus type I (HTLV-I)-infected T cells. Autoreactive T
cells from patients with HTLV-I-associated myelopathy/tropical spastic
paraparesis (HAM/TSP) spontaneously proliferate in vitro, and their
activation is reported to be associated with CD54 expression. The
spontaneous proliferation of T cells from patients with HAM/TSP was
entirely blocked by CI-959-A. However, in this study, the T-cell
proliferation in 15 patients with HAM/TSP was found to depend more
extensively on major histocompatibility complex (MHC) class II and CD86
than on CD54 Ags. Since most important APCs for the development of
HAM/TSP are DCs and HTLV-I-infected T cells, the effect of CI-959-A on
DC generation and on the expression of surface molecules on activated T
cells is examined. CI-959-A suppressed recombinant
granulocyte-macrophage colony stimulating factor (GM-CSF)- and
recombinant interleukin-4-dependent differentiation of DCs from
monocytes and inhibited the expression of CD54 and, more extensively,
MHC class II and CD86 Ags. CI-959-A showed little toxicity toward
lymphoma or HTLV-I-infected T-cell lines or toward monocytes and
cultured DCs. These results suggest that CI-959-A might be a potent
anti-HAM/TSP agent.Human T lymphotropic virus type I
(HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
is thought to be an autoimmune disease induced by HTLV-I infection
(8, 9, 24). The T lymphocytes obtained from patients with
HAM/TSP patients produce interleukin-2 (IL-2) in vivo and proliferate
spontaneously in vitro without any additional stimuli or cytokines
(35). This spontaneous proliferation of T lymphocytes (SPL)
depends on the interaction of T cells with antigen (Ag)-presenting
cells (APCs) such as dendritic cells (DCs) (17, 25) and
HTLV-I-infected CD4+ T cells (15, 32). The DCs
localized in the blood and nonlymphoid organs are considered to be
functionally immature, in that they are optimized for the uptake and
processing of Ag but not for the initiation of primary T-cell
responses. However, after the uptake of Ag and exposure to inflammatory
agents including tumor necrosis factor alpha (TNF-α) and IL-1, the
DCs undergo a process of maturation and gain the ability to present Ag
to T cells for their priming (22, 26). In addition to DCs,
HTLV-I-infected CD4+ T cells directly stimulate autologous
CD4+ T cells in a major histocompatibility complex (MHC)
class II- and CD86 molecule-dependent fashion (32). Among
the T cells stimulated with these APCs, some might cross-react with
self Ags and closely associate with the development of HAM/TSP.We have been searching for compounds that inhibit the cellular
interaction between APCs and T cells to suppress the activation of
autoreactive and Ag-specific T cells. The molecules associated with the
APC-T cell interaction may provide an effective target for therapy for
autoimmune diseases. Binding of APCs and T cells is initiated by
contact of adhesion molecules, such as CD54 and CD11a/CD18, expressed
on both cells, and induction of sustained proliferation of T cells
requires two independent signals provided by APCs: a T-cell
receptor-mediated Ag-specific signal and a signal mediated by
costimulatory molecules (CSMs) (10, 20) including CD86 and
CD58 Ags (1, 11, 31). Blocking of their tight binding
through adhesion molecules or interaction of the CSMs with CSM ligands
effectively suppressed the abnormal expansion of disease-associated T
cells in vivo and in vitro (19, 30, 32) and sometimes
effectively induced a long-term unresponsiveness of T cells to recall
stimuli.5-Methyl-3-(1-methylethoxy)benzo[b]thiophene-2-carbox-amide
(CI-959-A) is known to inhibit CD54 expression, and its derivative is
reported to inhibit casein kinase II (4). In the present
study, we found that CI-959-A markedly suppressed SPL in patients with
HAM/TSP. Furthermore, the compound suppressed the primary T-cell
proliferative response to stimuli provided by various APCs, the
differentiation of immature DCs from monocytes and their subsequent
maturation, and the induction of expression of MHC class II, CD54, and
CD86 Ags on activated CD4+ T cells. 相似文献
5.
Nakagawa M Suehara M Saito A Takashima H Umehara F Saito M Kanzato N Matsuzaki T Takenaga S Sakoda S Izumo S Osame M 《Neurology》1999,52(6):1271-1275
We found the association of a heterozygous novel MPZ gene point mutation, Ile62Phe in exon 2, with autosomal dominant motor and sensory neuropathy with focally folded myelin sheaths. Family study revealed that de novo Ile62Phe mutation on the MPZ gene occurred in the proband and was inherited by her children with early onset slowly progressive neuropathy. Our study suggests that the characteristic pathologic findings of the sural nerve in these patients are closely related to the site and nature of amino acid substitutions of the MPZ gene. 相似文献
6.
We investigated the localization and extent of beta-amyloid precursor protein (APP) immunoreactivity as a sensitive marker for impairment of fast axonal transport in the spinal cords of patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The results from this study show that APP, used as a marker of early axonal damage in HAM/TSP lesions, is more intensively expressed in areas of active-inflammatory lesions than those of inactive-chronic lesions. The close localization to the areas containing inflammation (activation of macrophage/microglia) is striking and suggests that axonal damage is closely associated with inflammation in active-chronic lesions. Although inflammatory cell infiltration in the central nervous system (CNS) is rarely found in inactive-chronic lesions, a few clusters of APP+ axons are found in the spinal cord white matter in some cases. The presence of APP+ axons without relation to inflammatory cells in inactive-chronic lesions, suggest that soluble neurotoxic factors might induce axonal changes in the CNS of HAM/TSP. The occasional myelinated fibers in the anterior and posterior spinal roots in lower thoracic to lumbar levels had APP+ axons, suggesting that spinal nerve roots can be affected in HAM/TSP, especially in lower thoracic to lumbar levels. Impairment of fast axonal transport may contribute to the development of disability in patients with HAM/TSP. 相似文献
7.
8.
Mayu Isotani Osamu Yamada Joshua L. Lachowicz Kyoichi Tamura Hiroko Yagihara Yasuhito Fujino Kenichiro Ono Tsukimi Washizu Makoto Bonkobara 《British journal of haematology》2010,148(1):144-153
The purpose of the current study was to investigate the mutation status of KIT in feline mast cell tumours (MCTs) and to examine the effects of tyrosine kinase inhibition on the phosphorylation of mutant kit in vitro and in clinical cases of cats. Sequence analysis of KIT identified mutations in 42/62 MCTs (67·7%). The vast majority of the mutations were distributed in exons 8 and 9, both of which encode the fifth immunoglobulin-like domain (IgD) of kit. All five types of kit with a mutation in the fifth IgD were then expressed in 293 cells and examined for phosphorylation status. The mutant kit proteins showed ligand-independent phosphorylation. The tyrosine kinase inhibitor imatinib mesylate suppressed the phosphorylation of these mutant kit proteins in transfectant cells. In a clinical study of 10 cats with MCTs, beneficial response to imatinib mesylate was observed in 7/8 cats that had a mutation in the fifth IgD of kit in tumour cells. Mutations in the fifth IgD of kit thus appear to be common and potentially sensitive to imatinib mesylate in feline MCTs. These data provide an in vivo model for paediatric mastocytosis where mutations in the fifth IgD of kit also occur. 相似文献
9.
Mayu Yazaki Takeru Nabeta Takayuki Inomata Kenji Maemura Takumi Oki Teppei Fujita Yuki Ikeda Shunsuke Ishii Takashi Naruke Yusuke Inoue Junya Ako 《Clinical cardiology》2021,44(2):222
BackgroundClinical significance of left atrial (LA) function and geometry in patients with dilated cardiomyopathy (DCM) remains uncertain.HypothesisLA geometric parameters assessed by cardiac magnetic resonance (CMR) predict the prognosis in patients with DCM.MethodsThe present study included patients with DCM and sinus rhythm who underwent CMR between December 2007 and April 2018. LA volume was measured using CMR. LA sphericity index was computed as the ratio of the measured maximum LA volume by the volume of a sphere with maximum LA length diameter.ResultsWe included 255 patients in this study. During the mean follow‐up of 3.92 years, hospitalization for HF occurred in 37 patients. The LA sphericity index was significantly higher in patients with hospitalization for HF than in those without (0.78 ± 0.35 vs. 0.58 ± 0.18, p < .001). Multivariable Cox regression analysis identified a higher LA sphericity index as an independent predictor of hospitalization for HF. Patients were categorized based on the median of LA sphericity index. The Kaplan–Meier curve showed that patients with a high LA sphericity index (≥0.57) had a significantly higher risk of hospitalization for HF than those with a low LA sphericity index (<0.57).ConclusionLA sphericity index was an independent predictor of hospitalization for HF. Assessment of LA geometric parameters might be useful for risk stratification in patients with DCM. 相似文献
10.