全文获取类型
收费全文 | 2588篇 |
免费 | 176篇 |
出版年
2023年 | 11篇 |
2021年 | 29篇 |
2020年 | 13篇 |
2019年 | 32篇 |
2018年 | 34篇 |
2017年 | 33篇 |
2016年 | 43篇 |
2015年 | 86篇 |
2014年 | 70篇 |
2013年 | 144篇 |
2012年 | 132篇 |
2011年 | 133篇 |
2010年 | 104篇 |
2009年 | 115篇 |
2008年 | 130篇 |
2007年 | 107篇 |
2006年 | 123篇 |
2005年 | 141篇 |
2004年 | 127篇 |
2003年 | 102篇 |
2002年 | 96篇 |
2001年 | 82篇 |
2000年 | 86篇 |
1999年 | 81篇 |
1998年 | 34篇 |
1997年 | 42篇 |
1996年 | 23篇 |
1995年 | 22篇 |
1994年 | 22篇 |
1993年 | 31篇 |
1992年 | 47篇 |
1991年 | 52篇 |
1990年 | 29篇 |
1989年 | 25篇 |
1988年 | 50篇 |
1987年 | 23篇 |
1986年 | 23篇 |
1985年 | 37篇 |
1984年 | 35篇 |
1983年 | 21篇 |
1982年 | 29篇 |
1981年 | 16篇 |
1980年 | 14篇 |
1979年 | 14篇 |
1978年 | 10篇 |
1975年 | 16篇 |
1974年 | 10篇 |
1972年 | 13篇 |
1969年 | 9篇 |
1968年 | 11篇 |
排序方式: 共有2764条查询结果,搜索用时 31 毫秒
101.
In this study, we studied the effects of cortisol and cortisone on the age-related decrease in locomotion in the nematode Caenorhabditis elegans and on the tolerance to heat stress at 35 °C and to oxidative stress induced by the exposure to 0.1% H2O2. Changes in mRNA expression levels of C. elegans genes related to stress tolerance were also analyzed. Cortisol treatment restored nematode movement following heat stress and increased viability under oxidative stress, but also shortened worm lifespan. Cortisone, a cortisol precursor, also restored movement after heat stress. Additionally, cortisol treatment increased mRNA expression of the hsp-12.6 and sod-3 genes. Furthermore, cortisol treatment failed to restore movement of daf-16-deficient mutants after heat stress, whereas cortisone failed to restore the movement of dhs-30-deficient mutants after heat stress. In conclusion, the results suggested that cortisol promoted stress tolerance via DAF-16 but shortened the lifespan, whereas cortisone promoted stress tolerance via DHS-30. 相似文献
102.
The signal produced by fluorescence in situ hybridization (FISH) often is inconsistent among cells and sensitivity is low. Small DNA targets on the chromatin are difficult to detect. We report here an improved nick translation procedure for Texas red and Alexa Fluor 488 direct labeling of FISH probes. Brighter probes can be obtained by adding excess DNA polymerase I. Using such probes, a 30?kb yeast transgene, and the rp1, rp3 and zein multigene clusters were clearly detected. 相似文献
103.
George Imataka Osamu Sakamoto Hideo Yamanouchi Shigemi Yoshihara Yuki Omura-Hasegawa Go Tajima Osamu Arisaka 《Cell biochemistry and biophysics》2013,67(1):185-187
We report herein a 1.5-year-old girl with methylmalonic acidemia (MMA) in whom two missense mutations were found: a novel I739T mutation located in exon 13 and the L494X mutation in exon 8. The results of organic acid test showed a pronounced increase in methylmalonate excretion with increased methylcitrate and 3-OH-propionate excretion, leading to a diagnosis of MMA, and Vitamin B12 administration was started. Analysis of the mut gene confirmed a T-to-A substitution at nucleotide position 1481 in exon 8 and a T-to-C substitution at nucleotide position 2216 in exon 13, leading to the amino acid isoleucine at position 739 being changed to threonine, resulting in c.2216T > C (p.I739T). The patient has now been on high-dose oral administration of Vitamin B12 and carnitine therapy (900 mg of levocarnitine chloride) for 5 years without experiencing further attacks, and her cognitive and motor development is normal. Further tests on residual enzyme activity, as well as experience with more cases, may shed light on the relationship between gene mutations and phenotypes in MMA. 相似文献
104.
S. Shibata Y. Sakamoto O. Baba C. Qin G. Murakami B.H. Cho 《European journal of histochemistry : EJH》2013,57(4)
Immunohistochemical localization of collagen types I, II, and X, aggrecan, versican, dentin matrix protein (DMP)-1, martix extracellular phosphoprotein (MEPE) were performed for Meckel’s cartilage, cranial base cartilage, and mandibular condylar cartilage in human midterm fetuses; staining patterns within the condylar cartilage were compared to those within other cartilaginous structures. Mandibular condylar cartilage contained aggrecan; it also had more type I collagen and a thicker hypertrophic cell layer than the other two types of cartilage; these three characteristics are similar to those of the secondary cartilage of rodents. MEPE immunoreactivity was first evident in the cartilage matrix of all types of cartilage in the human fetuses and in Meckel’s cartilage of mice and rats. MEPE immunoreactivity was enhanced in the deep layer of the hypertrophic cell layer and in the cartilaginous core of the bone trabeculae in the primary spongiosa. These results indicated that MEPE is a component of cartilage matrix and may be involved in cartilage mineralization. DMP-1 immunoreactivity first became evident in human bone lacunae walls and canaliculi; this pattern of expression was comparable to the pattern seen in rodents. In addition, chondroid bone was evident in the mandibular (glenoid) fossa of the temporal bone, and it had aggrecan, collagen types I and X, MEPE, and DMP-1 immunoreactivity; these findings indicated that chondroid bone in this region has phenotypic expression indicative of both hypertrophic chondrocytes and osteocytes.Key words: condylar cartilage, human fetus, extracellular matrix, MEPE, DMP-1 相似文献
105.
Takashi Sakamoto Akio Kobori Masako Shigezawa Yasutaka Amitani Maiko Higuchi Akira Murakami 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1659-1664
We developed a bispyrene-conjugated 2 ′-O-methyloligoribonucleotide as an RNA-specific RNA-probe. The probe hybridized with the complementary RNA, greatly enhancing fluorescence and discriminating RNA from DNA. The assay was carried out in homogeneous aqueous media without removing the unbound probe from the detection solution. This homogeneous fluorescence assay also discriminated mismatch sequences in the target RNA. These pyrene probes could possess high potential to detect RNA in biological specimens simply. 相似文献
106.
Yoshikazu Arai Jun Ohgane Shuh‐hei Fujishiro Kazuaki Nakano Hitomi Matsunari Masahito Watanabe Kazuhiro Umeyama Dai Azuma Naomi Uchida Nozomu Sakamoto Tomohiro Makino Shintaro Yagi Kunio Shiota Yutaka Hanazono Hiroshi Nagashima 《Genesis (New York, N.Y. : 2000)》2013,51(11):763-776
Porcine induced pluripotent stem cells (iPSCs) provide useful information for translational research. The quality of iPSCs can be assessed by their ability to differentiate into various cell types after chimera formation. However, analysis of chimera formation in pigs is a labor‐intensive and costly process, necessitating a simple evaluation method for porcine iPSCs. Our previous study identified mouse embryonic stem cell (ESC)‐specific hypomethylated loci (EShypo‐T‐DMRs), and, in this study, 36 genes selected from these were used to evaluate porcine iPSC lines. Based on the methylation profiles of the 36 genes, the iPSC line, Porco Rosso‐4, was found closest to mouse pluripotent stem cells among 5 porcine iPSCs. Moreover, Porco Rosso‐4 more efficiently contributed to the inner cell mass (ICM) of blastocysts than the iPSC line showing the lowest reprogramming of the 36 genes (Porco Rosso‐622‐14), indicating that the DNA methylation profile correlates with efficiency of ICM contribution. Furthermore, factors known to enhance iPSC quality (serum‐free medium with PD0325901 and CHIR99021) improved the methylation status at the 36 genes. Thus, the DNA methylation profile of these 36 genes is a viable index for evaluation of porcine iPSCs. genesis 51:763–776. © 2013 Wiley Periodicals, Inc. 相似文献
107.
108.
Christopher I Keeling Macaire MS Yuen Nancy Y Liao T Roderick Docking Simon K Chan Greg A Taylor Diana L Palmquist Shaun D Jackman Anh Nguyen Maria Li Hannah Henderson Jasmine K Janes Yongjun Zhao Pawan Pandoh Richard Moore Felix AH Sperling Dezene P W Huber Inanc Birol Steven JM Jones Joerg Bohlmann 《Genome biology》2013,14(3):R27
109.
110.
Hiroto Terasaki Satoru Kase Makoto Shirasawa Hiroki Otsuka Toshio Hisatomi Shozo Sonoda Susumu Ishida Tatsuro Ishibashi Taiji Sakamoto 《PloS one》2013,8(7)
Asymmetrical secretion of vascular endothelial growth factor (VEGF) by retinal pigment epithelial (RPE) cells in situ is critical for maintaining the homeostasis of the retina and choroid. VEGF is also involved in the development and progression of age-related macular degeneration (AMD). We studied the effect of tumor necrosis factor-α (TNF-α) on the secretion of VEGF in polarized and non-polarized RPE cells (P-RPE cells and N-RPE cells, respectively) in culture and in situ in rats. A subretinal injection of TNF-α caused a decrease in VEGF expression and choroidal atrophy. Porcine RPE cells were seeded on Transwell™ filters, and their maturation and polarization were confirmed by the asymmetrical VEGF secretion and trans electrical resistance. Exposure to TNF-α decreased the VEGF secretion in P-RPE cells but increased it in N-RPE cells in culture. TNF-α inactivated JNK in P-RPE cells but activated it in N-RPE cells, and TNF-α activated NF-κB in P-RPE cells but not in N-RPE cells. Inhibition of NF-κB activated JNK in both types of RPE cells indicating crosstalk between JNK and NF-κB. TNF-α induced the inhibitory effects of NF-κB on JNK in P-RPE cells because NF-κB is continuously inactivated. In N-RPE cells, however, it was not evident because NF-κB was already activated. The basic activation pattern of JNK and NF-κB and their crosstalk led to opposing responses of RPE cells to TNF-α. These results suggest that VEGF secretion under inflammatory conditions depends on cellular polarization, and the TNF-α-induced VEGF down-regulation may result in choroidal atrophy in polarized physiological RPE cells. TNF-α-induced VEGF up-regulation may cause neovascularization by non-polarized or non-physiological RPE cells. 相似文献