全文获取类型
收费全文 | 7450篇 |
免费 | 549篇 |
国内免费 | 692篇 |
出版年
2024年 | 15篇 |
2023年 | 86篇 |
2022年 | 119篇 |
2021年 | 398篇 |
2020年 | 299篇 |
2019年 | 347篇 |
2018年 | 323篇 |
2017年 | 266篇 |
2016年 | 359篇 |
2015年 | 498篇 |
2014年 | 562篇 |
2013年 | 612篇 |
2012年 | 762篇 |
2011年 | 642篇 |
2010年 | 362篇 |
2009年 | 365篇 |
2008年 | 387篇 |
2007年 | 329篇 |
2006年 | 288篇 |
2005年 | 238篇 |
2004年 | 206篇 |
2003年 | 175篇 |
2002年 | 152篇 |
2001年 | 151篇 |
2000年 | 115篇 |
1999年 | 100篇 |
1998年 | 68篇 |
1997年 | 71篇 |
1996年 | 67篇 |
1995年 | 54篇 |
1994年 | 49篇 |
1993年 | 31篇 |
1992年 | 41篇 |
1991年 | 20篇 |
1990年 | 25篇 |
1989年 | 19篇 |
1988年 | 16篇 |
1987年 | 16篇 |
1986年 | 11篇 |
1985年 | 18篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1966年 | 1篇 |
1965年 | 2篇 |
排序方式: 共有8691条查询结果,搜索用时 312 毫秒
991.
992.
993.
The phosphatidylinositol 3-kinase/AKT (PI3K/AKT) pathway plays a critical role in human cancer. We determined the expression
patterns of class I PI3K catalytic subunits and evaluated their importance in the development or progression of colorectal
cancer (CRC). For this purpose, expression of class I PI3K isoforms was evaluated in 82 primary CRC and paired non-cancerous
mucosa samples by qRT-PCR. P-AKT-Ser473 and P-AKT-Thr308 expression were measured by western blot. We found that, compared
with paired non-cancerous mucosa samples, mRNA expression of p110α and p110β in CRCs was significantly increased to 2.02-fold
(95% confidence interval [CI] 1.25–3.28 fold) and 1.76-fold (95% CI 1.19–2.60 fold), respectively; while slight differences
were found regarding the expression of p110δ (0.57-fold; 95% CI 0.31–1.07 fold) and p110γ (0.97-fold; 95% CI 0.50–1.88 fold).
Increased p110α and p110β expression correlated with primary tumor size, regional lymph node metastases, and AJCC stage. Increased
p110β expression also correlated with distant metastasis. P-AKT-Thr308 and P-AKT-Ser473 expression showed significant direct
correlations with p110α and p110β mRNA expression. Besides, CRC patients with p110β mRNA overexpression had a worse disease-free
survival after radical surgery compared with those with normal or decreased levels (P = 0.043). It was, therefore, concluded that the altered p110α and p110β expression might contribute to the CRC development
or progression. 相似文献
994.
Ochratoxin A (OTA) is nephrotoxic, immunosuppressive, and teratogenic in many species and is a possible human carcinogen. In this study, we investigated the OTA pollution situations of grains in northern China and the signaling pathway that mediated OTA-induced apoptosis in human tubular kidney cells (HKCs). Samples of grains collected from three representative areas were determined by using high-performance liquid chromatography fluorescence method. The effects of OTA on cell apoptosis, caspase-3, Bax, and Bcl-2 expression, and phosphorylation of c-Jun NH(2) terminal kinase (JNK) were detected in cultured HKCs via flow cytometry (FCM), Hoechst 33258 staining, and Western blot. It showed that OTA pollution of edible grains was very common in north China. OTA could affect caspase-3, Bax, and Bcl-2 expression and increased cell apoptosis in cultured HKCs. The JNK signalling pathway might play an important role during these cellular events. 相似文献
995.
Zhao X Chao Y Chen P Liu D Su P Sun J Cui X Tang Y 《Journal of physiology and biochemistry》2012,68(1):129-139
The 26S proteasome is a key component of the ubiquitin-proteasome system, a process responsible for the majority of cellular
protein degradation. The function of the proteasomal ubiquitin receptor hRpn13, a component of the 26S proteasome, is not
completely understood. To investigate the role of hRpn13 in the ubiquitin-proteasome system in osteoblasts, the effects of
suppressing and overexpressing the hRpn13 gene on proliferation, differentiation, and function of human osteoblast-like MG63
cells were examined. After knockdown of hRpn13 by small interfering RNA, changes in osteoblast proliferation were evaluated
by methyl-thiazolyl-tetrazolium assay. There was an increase in markers for osteoblast proliferation, specifically alkaline
phosphatase activity, and elevated protein levels of osteocalcin, proliferating cell nuclear antigen (PCNA), and ubiquitin.
Furthermore, hRpn13 knockdown also resulted in a decrease in the ratio between the gene expressions of RANKL and OPG, key
players in the pathogenesis of bone diseases that influence the normal balance between bone formation and resorption. In contrast,
overexpression of hRpn13 inhibited the proliferation of MG63 cells, and decreased alkaline phosphatase activity as well as
protein levels of osteocalcin, PCNA, and ubiquitin while the ratio of RANKL to OPG expression increased. To confirm the function
of hRpn13 in the ubiquitin-proteasome pathway, osteoblast proliferation enhancement and ubiquitin accumulation after hRpn2
knockdown was assessed. The results suggest that overexpression of hRpn13 negatively influences proliferation and osteogenic
differentiation in MG63 cells. The evidence implies that hRpn13 modulates the influence of osteoblasts on osteoclasts by controlling
the stability of regulatory proteins in osteoblasts. In summary, overexpression of hRpn13 promoted the activity of the ubiquitin-proteasome
system. 相似文献
996.
N Mao Y Ji Z Xie H Wang H Wang J An X Zhang Y Zhang Z Zhu A Cui S Xu K Shen C Liu W Yang W Xu 《PloS one》2012,7(8):e43893
The relevance of human parainfluenza viruses (HPIVs) to the epidemiology of acute respiratory infections (ARI) in China is unclear. From May 2008 to September 2010, 443 nasopharyngeal aspirates (NPAs) from hospitalized pediatric patients (age from 1 to 93 months) in Beijing were collected and screened for HPIVs and other common respiratory viruses by real-time RT-PCR. Sixty-two of 443 samples were positive for HPIVs with 4 positive for HPIV-2 and 58 positive for HPIV-3, indicating that HPIV-3 was the predominant virus present during the study period. A phylogenetic tree based on all the available HN (hemagglutinin-neuraminidase) sequences of HPIV-3 indicated that three distinct clusters (A,B, and C) were circulating with some temporal and regional clustering. Cluster C was further divided into sub-clusters, C1, C2, C3 and C4. HPIV-3 from Beijing isolates belonged to sub-cluster C3, and were grouped with the isolates from two Provinces of China and the neighboring country of Japan. Genetic analysis based on entire HN gene revealed that the HPIV-3 isolates from Beijing were highly similar with 97.2%-100% identity at the nucleotide level and these could be divided into two closely related lineages, C3a and C3b. These findings suggested that there was co-circulation of multiple lineages of HPIV-3 in the Beijing region during the study period. This is the first study to describe the epidemiology and molecular characterization of HPIVs in China. 相似文献
997.
A novel 'white' laccase was purified from the deuteromycete fungus, Myrothecium verrucaria NF-05, which was a high laccase-producing strain (40.2 U·ml(-1) on the thirteenth day during fermentation). SDS-PAGE and native-PAGE revealed a single band with laccase activity corresponding to a molecular weight of approximately 66 kDa. The enzyme had three copper and one iron atoms per protein molecule determined by ICP-AES. Furthermore, both UV/visible and EPR spectroscopy remained silence, indicating the enzyme a novel laccase with new metal compositions of active centre and spectral properties. The N-terminal amino acid sequence of the purified protein was APQISPQYPM. Together with MALDI-TOF analysis, the protein revealed a high homology of the protein with that from reported M. verrucaria. The highest activity was detected at pH 4.0 and at 30°C. The enzyme activity was significantly enhanced by Na(+), Mn(2+), Cu(2+) and Zn(2+) while inhibited by DTT, NaN(3) and halogen anions. The kinetic constant (Km) showed the enzyme was more affinitive to ABTS than other tested aromatic substrates. Twelve structurally different dyes could be effectively decolourised by the laccase within 10 min. The high production of the strain and novel properties of the laccase suggested its potential for biotechnological applications. 相似文献
998.
999.
1000.