全文获取类型
收费全文 | 20263篇 |
免费 | 2024篇 |
国内免费 | 1999篇 |
出版年
2024年 | 53篇 |
2023年 | 252篇 |
2022年 | 537篇 |
2021年 | 944篇 |
2020年 | 696篇 |
2019年 | 902篇 |
2018年 | 807篇 |
2017年 | 639篇 |
2016年 | 876篇 |
2015年 | 1290篇 |
2014年 | 1527篇 |
2013年 | 1611篇 |
2012年 | 1937篇 |
2011年 | 1719篇 |
2010年 | 1153篇 |
2009年 | 1024篇 |
2008年 | 1227篇 |
2007年 | 1112篇 |
2006年 | 1009篇 |
2005年 | 887篇 |
2004年 | 836篇 |
2003年 | 785篇 |
2002年 | 665篇 |
2001年 | 324篇 |
2000年 | 267篇 |
1999年 | 216篇 |
1998年 | 157篇 |
1997年 | 119篇 |
1996年 | 105篇 |
1995年 | 71篇 |
1994年 | 104篇 |
1993年 | 62篇 |
1992年 | 56篇 |
1991年 | 43篇 |
1990年 | 50篇 |
1989年 | 34篇 |
1988年 | 31篇 |
1987年 | 26篇 |
1986年 | 22篇 |
1985年 | 35篇 |
1984年 | 14篇 |
1983年 | 18篇 |
1982年 | 18篇 |
1981年 | 4篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1961年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 171 毫秒
11.
This study was conducted to investigate the prevalence of cognitive impairment, depression, and comorbidity of the two conditions and related factors in subjects aged in early 60s. This cross-sectional study included 3,174 inhabitants aged 60–64 years old in a rural area of Korea. Cognitive function was evaluated by the Korean version of the Mini-Mental State Examination (MMSE-K), and depression was measured using the short form of the Geriatric Depression Scale (GDS-15). The overall prevalence of cognitive impairment (MMSE-K≤24) was 17.4%, that of depression was 26.0% (GDS-15≥8), and the co-morbidity was 7.1%. Female gender, living with one housemate, and high GDS-15 score were significantly associated with increased cognitive impairment. Employment status and more years of schooling were associated with a decreased probability of cognitive impairment. Increased depression was significantly associated with bereavement and receiving benefits from the Medical Aid Program. Employed status, more years of schooling, and higher MMSE-K scores were significantly associated with decreased depression. The risk of comorbidity was associated with bereavement and receipt of Medical Aid benefits (odds ratio[OR], 1.85; 95% confidence interval[CI], 1.26–2.71; OR, 5.02; 95% CI, 2.37–10.63; respectively). Employment and more years of schooling were associated with a lower risk of comorbidity (OR, 0.46; 95% CI, 0.34–0.62, P-trend <0.01). The correlated factors for cognitive impairment, depression, and comorbidity of the two conditions were similar, and employment status and years of schooling were associated with all three conditions. 相似文献
12.
Bo Ram Kim Ji-Young Park Hyung Jae Jeong Hyung-Jun Kwon Su-Jin Park In-Chul Lee 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1256-1265
Sialidases are key virulence factors that remove sialic acid from the host cell surface glycan, unmasking receptors that facilitate bacterial adherence and colonisation. In this study, we developed potential agents for treating bacterial infections caused by Streptococcus pneumoniae Nan A that inhibit bacterial sialidase using Turmeric and curcumin analogues. Design, synthesis, and structure analysis relationship (SAR) studies have been also described. Evaluation of the synthesised derivatives demonstrated that compound 5e was the most potent inhibitor of S. pneumoniae sialidase (IC50?=?0.2?±?0.1?µM). This compound exhibited a 3.0-fold improvement in inhibitory activity over that of curcumin and displayed competitive inhibition. These results warrant further studies confirming the antipneumococcal activity 5e and indicated that curcumin derivatives could be potentially used to treat sepsis by bacterial infections. 相似文献
13.
Advanced hepatic fibrosis therapy using drug-delivering nanoparticles is a relatively unexplored area. Angiotensin type 1 (AT1) receptor blockers such as losartan can be delivered to hepatic stellate cells (HSC), blocking their activation and thereby reducing fibrosis progression in the liver. In our study, we analyzed the possibility of utilizing drug-loaded vehicles such as hyaluronic acid (HA) micelles carrying losartan to attenuate HSC activation. Losartan, which exhibits inherent lipophilicity, was loaded into the hydrophobic core of HA micelles with a 19.5% drug loading efficiency. An advanced liver fibrosis model was developed using C3H/HeN mice subjected to 20 weeks of prolonged TAA/ethanol weight-adapted treatment. The cytocompatibility and cell uptake profile of losartan-HA micelles were studied in murine fibroblast cells (NIH3T3), human hepatic stellate cells (hHSC) and FL83B cells (hepatocyte cell line). The ability of these nanoparticles to attenuate HSC activation was studied in activated HSC cells based on alpha smooth muscle actin (α-sma) expression. Mice treated with oral losartan or losartan-HA micelles were analyzed for serum enzyme levels (ALT/AST, CK and LDH) and collagen deposition (hydroxyproline levels) in the liver. The accumulation of HA micelles was observed in fibrotic livers, which suggests increased delivery of losartan compared to normal livers and specific uptake by HSC. Active reduction of α-sma was observed in hHSC and the liver sections of losartan-HA micelle-treated mice. The serum enzyme levels and collagen deposition of losartan-HA micelle-treated mice was reduced significantly compared to the oral losartan group. Losartan-HA micelles demonstrated significant attenuation of hepatic fibrosis via an HSC-targeting mechanism in our in vitro and in vivo studies. These nanoparticles can be considered as an alternative therapy for liver fibrosis. 相似文献
14.
Pasupathi Sundaramoorthy Jae Jun Sim Yeong-Su Jang Siddhartha Kumar Mishra Keun-Yeong Jeong Poonam Mander Oh Byung Chul Won-Sik Shim Seung Hyun Oh Ky-Youb Nam Hwan Mook Kim 《PloS one》2015,10(1)
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer. 相似文献
15.
Tissue plasminogen activator (tPA) has been implicated in neurite outgrowth and neurological recovery post stroke. tPA converts the zymogen plasminogen (Plg) into plasmin. In this study, using plasminogen knockout (Plg-/-) mice and their Plg-native littermates (Plg+/+), we investigated the role of Plg in axonal remodeling and neurological recovery after stroke. Plg+/+ and Plg-/- mice (n = 10/group) were subjected to permanent intraluminal monofilament middle cerebral artery occlusion (MCAo). A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the corticospinal tract (CST). Animals were euthanized 4 weeks after stroke. Neurite outgrowth was also measured in primary cultured cortical neurons harvested from Plg+/+ and Plg-/- embryos. In Plg+/+ mice, the motor functional deficiency after stroke progressively recovered with time. In contrast, recovery in Plg-/- mice was significantly impaired compared to Plg+/+ mice (p<0.01). BDA-positive axonal density of the CST originating from the contralesional cortex in the denervated side of the cervical gray matter was significantly reduced in Plg-/- mice compared with Plg+/+ mice (p<0.05). The behavioral outcome was highly correlated with the midline-crossing CST axonal density (R2>0.82, p<0.01). Plg-/- neurons exhibited significantly reduced neurite outgrowth. Our data suggest that plasminogen-dependent proteolysis has a beneficial effect during neurological recovery after stroke, at least in part, by promoting axonal remodeling in the denervated spinal cord. 相似文献
16.
The Korean species of the genus Eudorylas Aczél have been studied. A total of 16 species are arranged herein. Among them, E. paraappendiculatus sp. nov. is new to science, and E. nomurai Morakote et Yano, 1990 is newly recorded in the Korean fauna. 相似文献
17.
A heptageniid mayfly species Paegniodes dao sp. nov. (Ephemeroptera: Heptageniidae) is described from Vietnam. The larva is distinguished by round anterolateral margins of pronotum, triangular‐shaped labrum, rudimentary lamella and well developed fibrillae of gills 1, and light brown body that lacks distinct markings. Diagnosis, line drawings, material, and habitat data are provided. 相似文献
18.
Summary The production of 9-cis-1, 18-octadecenedioic acid from different substrates by the mutant S76 of Candida tropicalis was studied. It was found that the mutant could convert oleyl alcohol, oleic acid, and methyl oleate to 9-cis-1, 18-octadecenedioic acid through either the diterminal oxidation of the alcohol or the -oxidation of the terminal methyl group of the mono acid. The geometric configuration of the product was identified by different analytical methods. The results demonstrated that no change in the geometric configuration of molecular structure happened during the bioconversion of such unsaturated substrates to 9-dioic acid. To enhance the production of this dioic acid in the medium, calcium carbonate was added as a trapping agent. The IR spectrum, 1H NMR and 13C-satellite spectra of this compound were presented.Dedicated to Professor Dr. K. Esser on the occasion of his 65th birthday 相似文献
19.
Masanori Ito Kazuhiro Yoshida Eikai Kyo Ayse Ayhan Hirofumi Nakayama Wataru Yasui Hisao Ito Eiichi Tahara 《Virchows Archiv. B, Cell pathology including molecular pathology》1990,59(1):173-178
We have examined the expression of mRNAs for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-α), EGF
receptor (EGFR), PDGF-A chain (PDGFA), PDGF-B chain (PDGFB) and PDGF receptor (PDGFR) genes in seven human colorectal carcinoma
cell lines and 18 human colorectal carcinomas.
In surgically resected specimens of the 18 colorectal tumors, TGF-α, EGFR, PDGFA, PDGFB and PDGFR mRNAs were detected at various
levels in 15 (83%), 9 (50%), 18 (100%), 8 (44%) and 12 (67%), respectively. They were also detected in normal tissues. Interestingly,
EGF mRNA was detected in only five (28%) of the tumors, but not in normal mucosa. Expression of EGF was also confirmed immunohistochemically
in tumor cells. Of the five tumors expressing EGF, four expressed EGFR mRNA and showed a tendency to invade veins and lymphatics.
All the colorectal carcinoma cell lines expressed TGF-α mRNA, and five cell lines expressed EGFR mRNA simultaneously. Production
of TGF-α protein by DLD-1 and CoLo320DM cells was confirmed by TGF-α specific monoclonal antibody binding assay. The spontaneous3H-thymidine uptake by DLD-1 was suppressed by an anti-TGF-α monoclonal antibody. PDGFA and PDGFB mRNA were also expressed
in four cell lines, but PDGFR and EGF mRNA was not detected. These results suggest that human colorectal carcinomas express
multi-loops of growth factors and that TGF-α produced by tumor cells functions as an autocrine growth factor in human colonic
carcinoma. 相似文献
20.