全文获取类型
收费全文 | 4764篇 |
免费 | 434篇 |
国内免费 | 4篇 |
专业分类
5202篇 |
出版年
2022年 | 42篇 |
2021年 | 75篇 |
2020年 | 26篇 |
2019年 | 39篇 |
2018年 | 63篇 |
2017年 | 48篇 |
2016年 | 113篇 |
2015年 | 242篇 |
2014年 | 250篇 |
2013年 | 312篇 |
2012年 | 432篇 |
2011年 | 379篇 |
2010年 | 201篇 |
2009年 | 176篇 |
2008年 | 235篇 |
2007年 | 244篇 |
2006年 | 231篇 |
2005年 | 211篇 |
2004年 | 198篇 |
2003年 | 171篇 |
2002年 | 162篇 |
2001年 | 148篇 |
2000年 | 136篇 |
1999年 | 106篇 |
1998年 | 50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 | 59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5202条查询结果,搜索用时 10 毫秒
941.
942.
Preference tests have often been performed for collecting information about animals' acceptance of environmental refinement objects. In numerous published studies animals were individually tested during preference experiments, as it is difficult to observe group-housed animals with an automatic system. Thus, videotaping is still the most favoured method for observing preferences of socially-housed animals. To reduce the observation workload and to be able to carry out preference testing of socially-housed animals, an automatic recording system (DoubleCage) was developed for determining the location of group-housed animals in a preference test set-up. This system is able to distinguish the transition of individual animals between two cages and to record up to 16 animals at the same time (four animals per cage). The present study evaluated the reliability of the DoubleCage system. The data recorded by the DoubleCage program and the data obtained by human observation were compared. The measurements of the DoubleCage system and manual observation of the videotapes are comparable and significantly correlated (P < 0.0001) with good agreement. Using the DoubleCage system enables precise and reliable recording of the preferences of group-housed animals and a considerable reduction of animal observation time. 相似文献
943.
Mandal AK Zhang Z Kim SJ Tsai PC Mukherjee AB 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(10):6271-6273
For many years, cyclooxygenase-2 (COX-2), a critical enzyme for PG production, has been the favorite target for anti-inflammatory drug development. However, recent revelations regarding the adverse effects of selective COX-2 inhibitors have stimulated intense debate. Interestingly, in the early phase of inflammation, COX-2 facilitates inflammatory PG production while in the late phase it has anti-inflammatory effects. Moreover, although some PGs are proinflammatory, others have anti-inflammatory effects. Thus, it is likely that PGs with opposing effects maintain homeostasis, although the molecular mechanism(s) remains unclear. We report here that an inflammatory PG, PGD2, via its receptor, mediates the activation of NF-kappaB stimulating COX-2 gene expression. Most interestingly, an anti-inflammatory PG (PGA1) suppresses NF-kappaB activation and inhibits COX-2 gene expression. We propose that while pro- and anti-inflammatory PGs counteract each other to maintain homeostasis, selective COX-2 inhibitors may disrupt this balance, thereby resulting in reported adverse effects. 相似文献
944.
Huang YH Shih CM Huang CJ Lin CM Chou CM Tsai ML Liu TP Chiu JF Chen CT 《Journal of cellular biochemistry》2006,98(3):577-589
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder disease. Ten percent of the ALS patients are congenital (familial ALS), and the other 90% are sporadic ALS (SALS). It has been shown that mutations found in the Cu,Zn-SOD cause 20% of the familial ALS due to its low enzyme activity. We hypothesized that heavy metals may interfere the structure of Cu,Zn-SOD protein to suppress its activity in some of the SALS. In this study, we expressed and characterized the recombinant human Cu,Zn-SOD under various concentrations of Cu(2+), Zn(2+), and Cd(2+). By atomic absorption spectrophotometry, we demonstrated that adding of cadmium significantly increased the content of cadmium ion, but reduced its Zn(2+) content and enzyme activity of the Cu,Zn-SOD protein. The data of circular dichroism spectra demonstrated that the secondary structure of Cu,Zn-SOD/Cd is different from Cu,Zn-SOD, but close to apo-SOD. In addition to the effect of cadmium on Cu,Zn-SOD, cadmium was also shown to induce neural cell apoptosis. To further investigate the mechanism of neural cell apoptosis induced by cadmium, we used proteomics to analyze the altered protein expressions in neural cells treated with cadmium. The altered proteins include cellular structural proteins, stress-related and chaperone proteins, proteins involved in reactive oxygen species (ROS), enzyme proteins, and proteins that mediated cell death and survival signaling. Taken together, in this paper, we demonstrate that cadmium decreases the content of Zn(2+), changes the conformation of Cu,Zn-SOD protein to decrease its enzyme activity, and causes oxidative stress-induced neural cell apoptosis. 相似文献
945.
Qubo Zhu Lingjun Meng Joseph K. Hsu Tao Lin Jun Teishima Robert Y.L. Tsai 《The Journal of cell biology》2009,185(5):827-839
Telomeric repeat binding factor 1 (TRF1) is a component of the multiprotein complex “shelterin,” which organizes the telomere into a high-order structure. TRF1 knockout embryos suffer from severe growth defects without apparent telomere dysfunction, suggesting an obligatory role for TRF1 in cell cycle control. To date, the mechanism regulating the mitotic increase in TRF1 protein expression and its function in mitosis remains unclear. Here, we identify guanine nucleotide-binding protein-like 3 (GNL3L), a GTP-binding protein most similar to nucleostemin, as a novel TRF1-interacting protein in vivo. GNL3L binds TRF1 in the nucleoplasm and is capable of promoting the homodimerization and telomeric association of TRF1, preventing promyelocytic leukemia body recruitment of telomere-bound TRF1, and stabilizing TRF1 protein by inhibiting its ubiquitylation and binding to FBX4, an E3 ubiquitin ligase for TRF1. Most importantly, the TRF1 protein-stabilizing activity of GNL3L mediates the mitotic increase of TRF1 protein and promotes the metaphase-to-anaphase transition. This work reveals novel aspects of TRF1 modulation by GNL3L. 相似文献
946.
947.
948.
Rosemarie Swanson Ioannis Kagiampakis Jerry W Tsai 《Journal of computational biology》2008,15(1):65-79
We describe an information-theory-based measure of the quality of secondary structure prediction (RELINFO). RELINFO has a simple yet intuitive interpretation: it represents the factor by which secondary structure choice at a residue has been restricted by a prediction scheme. As an alternative interpretation of secondary structure prediction, RELINFO complements currently used methods by providing an information-based view as to why a prediction succeeds and fails. To demonstrate this score's capabilities, we applied RELINFO to an analysis of a large set of secondary structure predictions obtained from the first five rounds of the Critical Assessment of Structure Prediction (CASP) experiment. RELINFO is compared with two other common measures: percent correct (Q3) and secondary structure overlap (SOV). While the correlation between Q3 and RELINFO is approximately 0.85, RELINFO avoids certain disadvantages of Q3, including overestimating the quality of a prediction. The correlation between SOV and RELINFO is approximately 0.75. The valuable SOV measure unfortunately suffers from a saturation problem, and perhaps has unfairly given the general impression that secondary structure prediction has reached its limit since SOV hasn't improved much over the recent rounds of CASP. Although not a replacement for SOV, RELINFO has greater dispersion. Over the five rounds of CASP assessed here, RELINFO shows that predictions targets have been more difficult in successive CASP experiments, yet the predictions quality has continued to improve measurably over each round. In terms of information, the secondary structure prediction quality has almost doubled from CASP1 to CASP5. Therefore, as a different perspective of accuracy, RELINFO can help to improve prediction of protein secondary structure by providing a measure of difficulty as well as final quality of a prediction. 相似文献
949.
SRC-3/AIB1 is a steroid receptor coactivator with potent growth-promoting activity, and its overexpression is sufficient to induce tumorigenesis. Previous studies indicate that the cellular level of SRC-3 is tightly regulated by both ubiquitin-dependent and ubiquitin-independent proteasomal degradation pathways. Atypical protein kinase C (aPKC) is frequently overexpressed in cancers. In the present study, we show that aPKC phosphorylates and specifically stabilizes SRC-3 in a selective ER-dependent manner. We further demonstrate that an acidic residue-rich region in SRC-3 is an important determinant for aPKC-mediated phosphorylation and stabilization. The mechanism of the aPKC-mediated stabilization appears due to a decreased interaction between SRC-3 and the C8 subunit of the 20S core proteasome, thus preventing SRC-3 degradation. Our results demonstrate a potent signaling mechanism for regulating SRC-3 levels in cells by coordinate enzymatic inhibition of both ubiquitin-dependent and ubiquitin-independent proteolytic pathways. 相似文献
950.