全文获取类型
收费全文 | 4763篇 |
免费 | 439篇 |
国内免费 | 4篇 |
出版年
2022年 | 33篇 |
2021年 | 75篇 |
2020年 | 26篇 |
2019年 | 39篇 |
2018年 | 63篇 |
2017年 | 48篇 |
2016年 | 115篇 |
2015年 | 242篇 |
2014年 | 252篇 |
2013年 | 313篇 |
2012年 | 433篇 |
2011年 | 380篇 |
2010年 | 203篇 |
2009年 | 177篇 |
2008年 | 235篇 |
2007年 | 245篇 |
2006年 | 231篇 |
2005年 | 211篇 |
2004年 | 198篇 |
2003年 | 171篇 |
2002年 | 163篇 |
2001年 | 148篇 |
2000年 | 136篇 |
1999年 | 107篇 |
1998年 | 51篇 |
1997年 | 39篇 |
1996年 | 40篇 |
1995年 | 30篇 |
1994年 | 30篇 |
1993年 | 31篇 |
1992年 | 70篇 |
1991年 | 70篇 |
1990年 | 60篇 |
1989年 | 61篇 |
1988年 | 58篇 |
1987年 | 60篇 |
1986年 | 37篇 |
1985年 | 20篇 |
1984年 | 31篇 |
1983年 | 22篇 |
1982年 | 14篇 |
1981年 | 17篇 |
1979年 | 26篇 |
1978年 | 23篇 |
1977年 | 14篇 |
1976年 | 17篇 |
1975年 | 18篇 |
1974年 | 23篇 |
1973年 | 22篇 |
1972年 | 11篇 |
排序方式: 共有5206条查询结果,搜索用时 31 毫秒
151.
152.
Jeffrey M. Williams Takamasa Inoue Lindsey Banks Billy Tsai 《Molecular biology of the cell》2013,24(6):785-795
Cholera toxin (CT) traffics from the host cell surface to the endoplasmic reticulum (ER), where the toxin''s catalytic CTA1 subunit retrotranslocates to the cytosol to induce toxicity. In the ER, CT is captured by the E3 ubiquitin ligase Hrd1 via an undefined mechanism to prepare for retrotranslocation. Using loss-of-function and gain-of-function approaches, we demonstrate that the ER-resident factor ERdj5 promotes CTA1 retrotranslocation, in part, via its J domain. This Hsp70 cochaperone regulates binding between CTA and the ER Hsp70 BiP, a chaperone previously implicated in toxin retrotranslocation. Importantly, ERdj5 interacts with the Hrd1 adaptor Sel1L directly through Sel1L''s N-terminal lumenal domain, thereby linking ERdj5 to the Hrd1 complex. Sel1L itself also binds CTA and facilitates toxin retrotranslocation. By contrast, EDEM1 and OS-9, two established Sel1L binding partners, do not play significant roles in CTA1 retrotranslocation. Our results thus identify two ER factors that promote ER-to-cytosol transport of CTA1. They also indicate that ERdj5, by binding to Sel1L, triggers BiP–toxin interaction proximal to the Hrd1 complex. We postulate this scenario enables the Hrd1-associated retrotranslocation machinery to capture the toxin efficiently once the toxin is released from BiP. 相似文献
153.
I-Hui Yang Yao-Ting Tsai Siou-Jin Chiu Li-Teh Liu Hsuan-Hung Lee Ming-Feng Hou Wen-Li Hsu Ben-Kuen Chen Wei-Chiao Chang 《Journal of biomedical science》2013,20(1):41
Background
In non-excitable cells, one major route for calcium entry is through store-operated calcium (SOC) channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca2+ store. STIM1 and Orai1 are major regulators of SOC channels. In this study, we explored the functions of STIM1 and Orai1 in epidermal growth factor (EGF)-induced cell proliferation and migration in retinal pigment epithelial cells (ARPE-19 cell line).Results
EGF triggers cell proliferation and migration in ARPE-19 cells. Cell proliferation and migration involve STIM1 and Orai1, as well as phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, and Akt. Pharmacological inhibitors of SOC channels and siRNA of Orai1 and STIM1 suppress cell proliferation and migration. Pre-treatment of mitogen-activated protein kinase kinase (MEK) inhibitors and a phosphatidylinositol 3 kinases (PI3K) inhibitor attenuated cell proliferation and migration. However, inhibition of the SOC channels failed to prevent EGF-mediated ERK 1/2 and Akt phosphorylation.Conclusions
Our results showed that STIM1, Orai1, ERK 1/2, and Akt are key determinants of EGF-mediated cell growth in ARPE-19 cells. EGF is a potent growth molecule that has been linked to the development of PVR, and therefore, STIM1, Orai1, as well as the MEK/ERK 1/2 and PI3K/Akt pathways, might be potential therapeutic targets for drugs aimed at treating such disorders. 相似文献154.
Yu-Ting Wang Pei-Chien Tsai Yi-Chu Liao Chung-Y Hsu Suh-Hang Hank Juo 《Journal of biomedical science》2013,20(1):72
Background
The microRNAs let-7 g and miR-221 have been demonstrated to be related to the glucose metabolism. This study assessed the serum levels of these two microRNAs in subjects with and without metabolic syndrome (MetS).Results
The serum microRNA levels were detected in 102 subjects aged 40 to 80 years who were recruited from the general population. The status of MetS was defined by the Adult Treatment Panel III (ATP III) criteria modified for Asians. Subjects with histories of cardiovascular diseases or who were receiving treatment with hypoglycemic or lipid-lowering agents were excluded. The levels of both circulating microRNAs (let-7 g and miR-221) were higher in subjects with MetS (p = 0.004 and p = 0.01, respectively). The sex-specific analysis showed that the difference was more prominent in women (for both miRNAs, p < 0.05 in women and p > 0.1 in men). In the female subjects, increased expression of both microRNAs was associated with an increased number of MetS risk components (p = 0.002 for let-7 g and p = 0.022 for miR-221). Moreover, the elevation of serum let-7 g was significantly associated with a low level of high-density lipoprotein cholesterol (p = 0.022) and high blood pressure (p = 0.023). In contrast, the miR-221 level was not associated with any individual MetS risk component.Conclusions
The circulating levels of let-7 g and miR-221 displayed a female-specific elevation in individuals with metabolic syndrome. 相似文献155.
Jih-Jin Tsai Kulkanya Chokephaibulkit Po-Chih Chen Li-Teh Liu Hui-Mien Hsiao Yu-Chih Lo Guey Chuen Perng 《Journal of biomedical science》2013,20(1):88
Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis. 相似文献
156.
Pei-Lu Yi Chin-Yu Lu Chiung-Hsiang Cheng Yi-Fong Tsai Chung-Tien Lin Fang-Chia Chang 《Journal of biomedical science》2013,20(1):85
Background
Clinical and experimental evidence demonstrates that sleep and epilepsy reciprocally affect each other. Previous studies indicated that epilepsy alters sleep homeostasis; in contrast, sleep disturbance deteriorates epilepsy. If a therapy possesses both epilepsy suppression and sleep improvement, it would be the priority choice for seizure control. Effects of acupuncture of Feng-Chi (GB20) acupoints on epilepsy suppression and insomnia treatment have been documented in the ancient Chinese literature, Lingshu Jing (Classic of the Miraculous Pivot). Therefore, this study was designed to investigate the effect of electroacupuncture (EA) stimulation of bilateral Feng-Chi acupoints on sleep disruptions in rats with focal epilepsy.Results
Our result indicates that administration of pilocarpine into the left central nucleus of amygdala (CeA) induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep. High-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints, in which a 30-min EA stimulation was performed before the dark period of the light:dark cycle in three consecutive days, further deteriorated pilocarpine-induced sleep disruptions. The EA-induced exacerbation of sleep disruption was blocked by microinjection of naloxone, μ- (naloxonazine), κ- (nor-binaltorphimine) or δ-receptor antagonists (natrindole) into the CeA, suggesting the involvement of amygdaloid opioid receptors.Conclusion
The present study suggests that high-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints exhibits no benefit in improving pilocarpine-induced sleep disruptions; in contrast, EA further deteriorated sleep disturbances. Opioid receptors in the CeA mediated EA-induced exacerbation of sleep disruptions in epileptic rats. 相似文献157.
J. Jamison J. Gilloteaux M. R. Nassiri C. C. Tsai J. Summers 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1221-1222
Abstract Magnesium (Mg2+) potentiated the anti-vesicular stomatitis virus (VSV) activity of poly r(A-U) or poly r(G-C) and the anti-HIV-1 activity of poly r(A-U). Mg2+ did not affect the anti-VSV activity of poly (rI) ? poly (rC), poly (dA-dT) ? poly (dA-dT) or poly (dG-dC) ? poly (dG-dC). Modulation of one or more nuclear (nucleolar) processes of the host cell may be responsible for the synergistic antiviral activity. 相似文献
158.
Alexander C. Tsai Jennifer A. Scott Kristin J. Hung Jennifer Q. Zhu Lynn T. Matthews Christina Psaros Mark Tomlinson 《PloS one》2013,8(12)
Background
A major barrier to improving perinatal mental health in Africa is the lack of locally validated tools for identifying probable cases of perinatal depression or for measuring changes in depression symptom severity. We systematically reviewed the evidence on the reliability and validity of instruments to assess perinatal depression in African settings.Methods and Findings
Of 1,027 records identified through searching 7 electronic databases, we reviewed 126 full-text reports. We included 25 unique studies, which were disseminated in 26 journal articles and 1 doctoral dissertation. These enrolled 12,544 women living in nine different North and sub-Saharan African countries. Only three studies (12%) used instruments developed specifically for use in a given cultural setting. Most studies provided evidence of criterion-related validity (20 [80%]) or reliability (15 [60%]), while fewer studies provided evidence of construct validity, content validity, or internal structure. The Edinburgh postnatal depression scale (EPDS), assessed in 16 studies (64%), was the most frequently used instrument in our sample. Ten studies estimated the internal consistency of the EPDS (median estimated coefficient alpha, 0.84; interquartile range, 0.71-0.87). For the 14 studies that estimated sensitivity and specificity for the EPDS, we constructed 2 x 2 tables for each cut-off score. Using a bivariate random-effects model, we estimated a pooled sensitivity of 0.94 (95% confidence interval [CI], 0.68-0.99) and a pooled specificity of 0.77 (95% CI, 0.59-0.88) at a cut-off score of ≥9, with higher cut-off scores yielding greater specificity at the cost of lower sensitivity.Conclusions
The EPDS can reliably and validly measure perinatal depression symptom severity or screen for probable postnatal depression in African countries, but more validation studies on other instruments are needed. In addition, more qualitative research is needed to adequately characterize local understandings of perinatal depression-like syndromes in different African contexts. 相似文献159.
Ching-Hui Huang Chia-Chu Chang Ching-Shan Huang Chen-Ling Kuo Ching-Pei Chen Chien-Hsun Hsia Yung-Ming Chang Hung-Te Chen Chih-Chung Feng Lee-Shin Lin Po-Ta Yang Chen-Dao Tsai Chih-Sheng Lin Chin-San Liu 《PloS one》2013,8(10)
Objectives
Oxidized low-density lipoproteins (oxLDL) and oxidized low-density lipoprotein autoantibodies (OLAB) have been detected in human plasma and atherosclerotic lesions. OLAB appear to play a role in the clearance of oxLDL from circulation. Higher levels of OLAB appear to be associated with a reduced risk of a wide range of cardiovascular diseases. We investigated the prognostic value of plasma oxLDL and OLAB in patients undergoing primary coronary balloon angioplasty for acute ST-elevation myocardial infarction (STEMI).Methods
Plasma oxLDL and OLAB concentrations were measured in 56 patients with acute STEMI before primary angioplasty, and then 3 days, 7 days and 1 month after the acute event. Follow-up angiography was repeated 6 months later to detect the presence of restensosis (defined as >50% luminal diameter stenosis). The thrombolysis in myocardial infarction (TIMI) risk score was calculated to determine the relationship between OLAB/oxLDL ratio and TIMI risk scores.Results
Of the 56 patients, 18 (31%) had angiographic evidence of restenosis. Plasma OLAB concentrations were significantly lower in the restenosis group before angioplasty (181±114 vs. 335±257 U/L, p = 0.003), and at day 3 (155±92 vs. 277±185 U/L, p<0.001) and day 7 (177±110 vs. 352±279 U/L, p<0.001) after the acute event. There was no difference in oxLDL concentration between the two groups. The ratio of OLAB/oxLDL positively correlated with TIMI risk scores before angioplasty (p for trend analysis, p = 0.004), at day 3 (p = 0.008) and day 7 (p<0.001) after STEMI.Significance
A relative deficit of OLAB, and hence likely impaired clearance of oxLDL, is associated with the risk of arterial restenosis after primary angioplasty for acute STEMI. 相似文献160.