全文获取类型
收费全文 | 1285篇 |
免费 | 70篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 11篇 |
儿科学 | 42篇 |
妇产科学 | 18篇 |
基础医学 | 132篇 |
口腔科学 | 64篇 |
临床医学 | 74篇 |
内科学 | 404篇 |
皮肤病学 | 15篇 |
神经病学 | 64篇 |
特种医学 | 54篇 |
外科学 | 288篇 |
综合类 | 9篇 |
预防医学 | 23篇 |
眼科学 | 3篇 |
药学 | 43篇 |
中国医学 | 3篇 |
肿瘤学 | 114篇 |
出版年
2023年 | 5篇 |
2022年 | 14篇 |
2021年 | 24篇 |
2020年 | 22篇 |
2019年 | 25篇 |
2018年 | 35篇 |
2017年 | 20篇 |
2016年 | 27篇 |
2015年 | 40篇 |
2014年 | 54篇 |
2013年 | 48篇 |
2012年 | 73篇 |
2011年 | 91篇 |
2010年 | 38篇 |
2009年 | 51篇 |
2008年 | 98篇 |
2007年 | 87篇 |
2006年 | 83篇 |
2005年 | 97篇 |
2004年 | 97篇 |
2003年 | 88篇 |
2002年 | 80篇 |
2001年 | 8篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 12篇 |
1995年 | 10篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1969年 | 2篇 |
1967年 | 2篇 |
1960年 | 2篇 |
排序方式: 共有1361条查询结果,搜索用时 15 毫秒
1.
2.
Einosuke Mizuta Toshihiro Hamada Shin-ichi Taniguchi Masaki Shimoyama Takahiro Nawada Junichiro Miake Yasuhiro Kaetsu Li Peili Kiyosuke Ishiguro Shingo Ishiguro Osamu Igawa Chiaki Shigemasa Ichiro Hisatome 《Hypertension research》2006,29(8):635-638
We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ?) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients. 相似文献
3.
4.
Kazuhiko Sonoyama Haruaki Ninomiya Osamu Igawa Yasuhiro Kaetsu Yoshiyuki Furuse Toshihiro Hamada Junichiro Miake Peili Li Yasutaka Yamamoto Kazuhide Ogino Akio Yoshida Shin-ichi Taniguchi Yasutaka Kurata Satoshi Matsuoka Toshio Narahashi Goshi Shiota Yoshihisa Nozawa Hiroaki Matsubara Masatsugu Horiuchi Yasuaki Shirayoshi Ichiro Hisatome 《Hypertension research》2006,29(11):923-934
We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells. 相似文献
5.
Kawano Y Fukuda J Itoh H Takai N Nasu K Miyakawa I 《American journal of reproductive immunology (New York, N.Y. : 1989)》2004,52(2):124-128
PROBLEM: In order to investigate the role of macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein -1 (MCP-1) in human ovulation, we studied the regulation of M-CSF and MCP-1 in cultured human granulosa cells. METHOD OF STUDY: Immortalized granulosa cells (GC1a) were cultured in serum-free medium, and incubated with interleukin (IL)-1alpha, IL-1 receptor antagonist (ra) and tumor necrosis factor (TNF)-alpha. The supernatants were collected, and M-CSF and MCP-1 were measured by ELISA. RESULTS: The levels of M-CSF and MCP-1 were increased after treatment with IL-1alpha (1 nm) and TNF-alpha (1 nm) in a time-dependent manner. The levels of M-CSF and MCP-1 were significantly increased after treatment with IL-1alpha and TNF-alpha in a dose-dependent manner. However, the levels of M-CSF and MCP-1 were significantly decreased by treatment with IL-1alpha (1 nm) and/or increasing concentrations of IL-1 ra. CONCLUSIONS: Our data indicated that M-CSF and MCP-1 were regulated by IL-1alpha and TNF-alpha. It was suggested that M-CSF and MCP-1 may play an important role in human preovulatory processes. 相似文献
6.
Kai K Nasu K Nakamura S Fukuda J Nishida M Miyakawa I 《Molecular human reproduction》2002,8(2):176-180
Human endometrial stromal cells (ESC) can produce a variety of chemokines, especially after inflammatory stimulation. Interferon-gamma-inducible protein-10 (IP-10) is a potent chemoattractant for lymphocytes, and belongs to the family of non-ELR CXC chemokines. The expression of IP-10 in ESC after stimulation with interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), or lipopolysaccharide (LPS) was evaluated using an enzyme-linked immunosorbent assay and Northern blot analysis. A small amount of IP-10 protein was detected in the culture media of unstimulated ESC. The expression of IP-10 mRNA was detected in ESC. IFN-gamma, IL-1 beta, TNF-alpha and LPS significantly stimulated the expression of IP-10 mRNA and protein in ESC. These results suggest that the production of IP-10 by ESC is regulated by inflammatory mediators. The modulation of IP-10 concentrations in the local environment may contribute to the normal and pathological processes of human reproduction by regulating leukocyte trafficking in the endometrium. 相似文献
7.
Atsuo Ogura Toshihiko Asano Junichiro Matsuda Minako Koura Masaro Nakagawa Hiroshi Kawaguchi Yutaka Yamaguchi 《Virchows Archiv : an international journal of pathology》1990,417(3):223-228
Summary Glomerular lesions in hereditary nephrotic mice (ICGN strain) were investigated by electron microscopy. The glomeruli of unaffected animals, which appeared normal by light microscopy, had developed an ultrastructural change in the glomerular capillary basement membrane (GCBM). There was a partial thickening of the GCBM with bilaminar splitting of the lamina densa and an electron-dense fibrillar material exhibiting cross-striations. In affected animals, light microscopy revealed a marked thickening of GCBM and an increase of mesangial matrix without cellular proliferaton. By electron microscopy, multilaminar splitting of the lamina densa in the thickened GCBMs and fusion of the epithelial foot processes were observed. In some severely affected animals, immune complex deposition was found in GCBM, but little if any was observed in other animals. In the end, the glomeruli were globally sclerosed. Our findings suggest that initial structural abnormalities in GCBM may play an important role in the onset and development of the disease, though subsequent events such as immune complex deposition would modify the disease. 相似文献
8.
Ohisa N Hashimoto J Yoshida K Imai Y Kaku M 《Rinsho byori. The Japanese journal of clinical pathology》2005,53(3):195-200
The circadian variation of blood pressure (BP) may be mediated at least in part by circadian variation of autonomic nervous system activity. In the present study power spectral analysis of hourly R-R intervals for 24 hours was done to obtain the low frequency variability (LF: 0.04 to 0.15Hz) and high frequency variability(HF: 0.15 to 0.40Hz) in 93 patients with untreated essential hypertension. LF/HF ratio and HF were considered to be an index of sympathetic nervous activity and parasympathetic nervous activity, respectively. The relationship between heart rate (HR) and systolic blood pressure (SBP), diastolic blood pressure (DBP), HF, and LF/HF was examined. Both SBP and DBP were correlated positively with HR(r = 0.28, p < 0.05 and r = 0.27, p < 0.05, respectively) in the daytime. HF was correlated negatively and significantly with HR in both daytime and nighttime (r = -0.40, p < 0.05, and r = -0.38, p < 0.05 respectively). After averaging for SBP of 24 hours, HR in the patients whose SBP was 135mmHg or more was significantly higher than that in the patients whose SBP was less than 135mmHg. These results suggest that the decreased parasympathetic nervous activity seems to be responsible for the rise in BP. 相似文献
9.
Katagiri YU Ohmi K Tang W Takenouchi H Taguchi T Kiyokawa N Fujimoto J 《Laboratory investigation; a journal of technical methods and pathology》2002,82(12):1735-1745
SUMMARY: Raft microdomains are glycolipid-enriched microdomain scaffolding molecules involved in signal transduction. The binding of Shiga toxin to globotriaosyl ceramide in raft microdomains of the human renal tubular cell line ACHN causes temporal activation of Src-kinase Yes. To study the downstream signaling mechanism proceeding to the activation of Yes, we raised monoclonal antibodies (MAbs) against raft microdomains. The MAbs were screened on the basis of, first, binding to raft microdomains with dot-blot immunostaining, second, intracellular localization of the epitope by flowcytometry after permeabilization, and third, translocation of the antigen molecules after Stx treatment by immunohistochemical staining. Raft.1 MAb bound to the molecules that accumulated to the particular region near the nucleus after Stx treatment. Two-dimensional Western blotting and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis revealed that the antigen molecule is GTP binding protein beta subunits 1 and 2 (Gbeta1 and 2). That Raft.1 recognized Gbeta1 and 2 was further confirmed by the reactivity to recombinant Gbeta1 and 2 proteins. To our knowledge, this is the first report of production of a MAb recognizing Gbeta1 and 2. Because Gbeta1 and 2 are highly conserved all through organisms and are deeply involved in signal transduction, Raft.1 is expected to be utilized frequently in research. 相似文献
10.
Hideo Tanaka Yoshizumi Habuchi Taku Yamamoto Manabu Nishio Junichiro Morikawa Manabu Yoshimura 《British journal of pharmacology》1997,122(2):321-329
- The effects of endothelin-1 (ET-1) on sinoatrial (SA) node preparations of the rabbit heart were studied by means of whole-cell clamp techniques.
- ET-1 at 1 nM slowed the spontaneous beating activity and rendered half of the cells quiescent. At a higher concentration of 10 nM, the slowing and cessation of spontaneous activity were accompanied by hyperpolarization.
- In voltage-clamp experiments, ET-1 decreased the basal L-type Ca2+ current (ICa(L)) dose-dependently with a half-maximal inhibitory concentration (EC50) of 0.42 nM and maximal inhibitory response (Emax) of 49.5%. The delayed rectifying K+ current (IK) was also reduced by 33.2±11.1% at 1 nM. In addition, an inwardly rectifying K+ current was activated by ET-1 at higher concentrations (EC50=4.8 nM). These ET-1-induced changes in membrane currents were abolished by BQ485 (0.3 μM), a highly selective ETA receptor antagonist.
- When ICa(L) was inhibited by ET-1 (1 nM), subsequent application of 10 μM ACh showed no additional decrease in ICa(L), suggesting the involvement of cyclic AMP in the effects of ET-1 on ICa(L). In contrast, 1 nM ET-1 further decreased ICa(L) in the presence of 10 μM ACh, suggesting that ET-1 activates some additional mechanism(s) which inhibit ICa(L). The ET-1-induced ICa(L) inhibition was abolished by protein kinase A inhibitory peptide (PKI, 20 μM) or H-89 (5 μM). However, the ICa(L) inhibition was not affected by methylene blue (10 μM), suggesting a minor role for cyclic GMP in the effect of ET-1 under basal conditions.
- ET-1 failed to inhibit ICa(L) when the pipette contained GDPβS (200 μM). However, incubation of the cells with pertussis toxin (PTX, 5 μg ml−1, >6 h) only reduced the ET-1-induced inhibition to 21.5±9.5%, whereas it abolished the inhibitory effect of ACh on ICa(L).
- Intracellular perfusion of 8-bromo cyclicAMP (8-Br cyclicAMP, 500 μM) attenuated, but did not abolish the inhibitory effect of ET-1 on ICa(L). This 8-Br cyclicAMP-resistant component (17.5±14.4%, n=20) was not affected by combined application of 8-Br cyclicAMP with 8-bromo cyclicGMP (500 μM), ryanodine (1 μM) or phorbol-12-myristate-13-acetate (TPA; 50 nM).
- In summary, ET-1 exerts negative chronotropic effects on the SA node via ETA-receptors. ET-1 inhibits both ICa(L) and IK, and increases background K+ current. The inhibition of ICa(L) by ET-1 is mainly due to reduction of the cyclicAMP levels via PTX-sensitive G protein, but some other mechanism(s) also seems to be operative.