全文获取类型
收费全文 | 6063篇 |
免费 | 286篇 |
国内免费 | 7篇 |
专业分类
6356篇 |
出版年
2022年 | 42篇 |
2021年 | 64篇 |
2020年 | 31篇 |
2019年 | 50篇 |
2018年 | 90篇 |
2017年 | 59篇 |
2016年 | 125篇 |
2015年 | 172篇 |
2014年 | 203篇 |
2013年 | 526篇 |
2012年 | 353篇 |
2011年 | 380篇 |
2010年 | 228篇 |
2009年 | 236篇 |
2008年 | 392篇 |
2007年 | 413篇 |
2006年 | 368篇 |
2005年 | 409篇 |
2004年 | 388篇 |
2003年 | 412篇 |
2002年 | 326篇 |
2001年 | 57篇 |
2000年 | 31篇 |
1999年 | 67篇 |
1998年 | 88篇 |
1997年 | 72篇 |
1996年 | 63篇 |
1995年 | 54篇 |
1994年 | 56篇 |
1993年 | 60篇 |
1992年 | 45篇 |
1991年 | 36篇 |
1990年 | 39篇 |
1989年 | 24篇 |
1988年 | 28篇 |
1987年 | 16篇 |
1986年 | 17篇 |
1985年 | 24篇 |
1984年 | 23篇 |
1983年 | 20篇 |
1982年 | 31篇 |
1981年 | 48篇 |
1980年 | 31篇 |
1979年 | 20篇 |
1978年 | 13篇 |
1977年 | 15篇 |
1976年 | 14篇 |
1975年 | 18篇 |
1973年 | 12篇 |
1972年 | 10篇 |
排序方式: 共有6356条查询结果,搜索用时 0 毫秒
51.
Hitomi Yatsuki Ken Higashimoto Kosuke Jozaki Kayoko Koide Junichiro Okada Yoriko Watanabe Nobuhiko Okamoto Yoshinobu Tsuno Yoko Yoshida Kazutoshi Ueda Kenji Shimizu Hirofumi Ohashi Tsunehiro Mukai Hidenobu Soejima 《Genes & genomics.》2013,35(2):141-147
Beckwith-Wiedemann syndrome (BWS) is an imprinting-related human disease that is characterized by macrosomia, macroglossia, abdominal wall defects, and variable minor features. BWS is caused by several genetic/epigenetic alterations, such as loss of methylation at KvDMR1, gain of methylation at H19-DMR, paternal uniparental disomy of chromosome 11, CDKN1C mutations, and structural abnormalities of chromosome 11. CDKN1C is an imprinted gene with maternal preferential expression, encoding for a cyclin-dependent kinase (CDK) inhibitor. Mutations in CDKN1C are found in 40 % of familial BWS cases with dominant maternal transmission and in ~5 % of sporadic cases. In this study, we searched for CDKN1C mutations in 37 BWS cases that had no evidence for other alterations. We found five mutations—four novel and one known—from a total of six patients. Four were maternally inherited and one was a de novo mutation. Two frame-shift mutations and one nonsense mutation abolished the QT domain, containing a PCNA-binding domain and a nuclear localization signal. Two missense mutations occurred in the CDK inhibitory domain, diminishing its inhibitory function. The above-mentioned mutations were predicted by in silico analysis to lead to loss of function; therefore, we strongly suspect that such anomalies are causative in the etiology of BWS. 相似文献
52.
Dan Chen Satoko Ito Hong Yuan Toshinori Hyodo Kenji Kadomatsu Michinari Hamaguchi Takeshi Senga 《Cell cycle (Georgetown, Tex.)》2015,14(10):1529-1539
Echinoderm microtubule-associated protein (EMAP)-like (EML) family proteins are microtubule-associated proteins that have a conserved hydrophobic EMAP-like protein (HELP) domain and multiple WD40 domains. In this study, we examined the role of EML4, which is a member of the EML family, in cell division. Time-lapse microscopy analysis demonstrated that EML4 depletion induced chromosome misalignment during metaphase and delayed anaphase initiation. Further analysis by immunofluorescence showed that EML4 was required for the organization of the mitotic spindle and for the proper attachment of kinetochores to microtubules. We searched for EML4-associating proteins by mass spectrometry analysis and found that the nuclear distribution gene C (NUDC) protein, which is a critical factor for the progression of mitosis, was associated with EML4. This interaction was mediated by the WD40 repeat of EML4 and by the C-terminus of NUDC. In the absence of EML4, NUDC was no longer able to localize to the mitotic spindle, whereas NUDC was dispensable for EML4 localization. Our results show that EML4 is critical for the loading of NUDC onto the mitotic spindle for mitotic progression. 相似文献
53.
54.
55.
Nagahata H Higuchi H Teraoka H Takahashi K Takahashi K Kuwabara M Inanami O Kuwabara M 《Immunology and cell biology》2004,82(1):32-37
Stimulant-induced viability of neutrophils, nuclear-fragmentation, increase in intracellular calcium ([Ca2+]i), expression of annexin V on neutrophils and proteolysis of a fluorogenic peptide substrate Ac-DEVD-MCA (acetyl Asp-Glu-Val-Asp alpha-[4-methyl-coumaryl-7-amide]) by neutrophil lysates from five normal calves and three calves with leucocyte adhesion deficiency were determined to evaluate the apoptosis of normal and CD18-deficient neutrophils. Viability was markedly decreased in control neutrophils stimulated with opsonized zymosan (OPZ), compared to CD18-deficient neutrophils at 37 degrees C after incubation periods of 6 and 24 hours. The rate of apoptosis of control neutrophils stimulated with OPZ increased significantly depending on the incubation time, whereas no apparent increase in apoptosis was found in CD18-deficient neutrophils under the same conditions. Aggregated bovine (Agg) IgG-induced apoptosis of control neutrophils was not significantly different from that of CD18-deficient neutrophils. The expression of annexin V on OPZ-stimulated control neutrophils was greater than that of unstimulated ones 6 h after stimulation. No apparent increase in annexin V expression on CD18-deficient neutrophils was found with OPZ stimulation. A delay in apoptosis was demonstrated in CD18-deficient bovine neutrophils and this appeared to be closely associated with lowered signalling via [Ca2+]i, diminished annexin V expression on the cell surface, and decreased caspase 3 activity in lysates. 相似文献
56.
57.
Ishizuka Y Fujiwara M Kanazawa K Nemoto T Fujita K Nakanishi H 《Carbohydrate research》2002,337(19):1737-1743
The inclusion of phloridzin into beta-cyclodextrin was studied as a model of molecular recognition in membranes. Effects on 1H NMR spectra and NOE correlational peaks between phloridzin and beta-cyclodextrin were observed in the complex. Strong NOEs were observed between hydrogens of a phenol group in phloridzin and beta-cyclodextrin. The three-dimensional structure of the inclusion complex between phloridzin and beta-cyclodextrin was simulated with distance constraints estimated by the intensity of NOE peaks using the DADAS90 programs. Two inclusion possibilities were suggested-the large rim of beta-cyclodextrin as an entrance of the inclusion and the small rim of beta-cyclodextrin as the entrance. In both cases, the phenol group of phloridzin was included in the hydrophobic space of beta-cyclodextrin. 相似文献
58.
Shimoda K Kamesaki K Numata A Aoki K Matsuda T Oritani K Tamiya S Kato K Takase K Imamura R Yamamoto T Miyamoto T Nagafuji K Gondo H Nagafuchi S Nakayama K Harada M 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(9):4707-4711
IFN-alpha inhibits B lymphocyte development, and the nuclear protein Daxx has been reported to be essential for this biological activity. We show in this study that IFN-alpha inhibits the clonal proliferation of B lymphocyte progenitors in response to IL-7 in wild-type, but not in tyk2-deficient, mice. In addition, the IFN-alpha-induced up-regulation and nuclear translocation of Daxx are completely abrogated in the absence of tyk2. Therefore, tyk2 is directly involved in IFN-alpha signaling for the induction and translocation of Daxx, which may result in B lymphocyte growth arrest and/or apoptosis. 相似文献
59.
Hormonal regulation of fruit set, parthenogenesis induction and fruit expansion in Japanese pear 总被引:2,自引:1,他引:2
The effects of applied gibberellins (GAs), GA1, GA3, GA4 and GA7 with a cytokinin, N-(2-chloro-4-pyridyl)-N′-phenylurea (CPPU) and indole-3-acetic acid (IAA) on fruit set, parthenogenesis induction and fruit expansion of a number
of Rosaceae species were assessed. These included Japanese pear cv. ‘Akibae’ (self-compatible) and cv. ‘Iwate yamanashi’ (a
seedless cultivar). Other Rosaceae species (Pyrus communis, Chaenomeles sinensis, Cydonia oblonga, and Malus pumila) were also investigated. GA4, GA7 and CPPU are very effective in inducing parthenocarpic fruit growth, whereas GA1, GA3 and IAA, have no ability to induce parthenogenesis in Japanese pear. GA4- and GA7-induced parthenocarpic fruit tended to be smaller in size, higher in flesh hardness, and showed advanced fruit ripening in
comparison to pollinated fruit and to parthenocarpic fruit induced by CPPU. GA4- and GA7-induced parthenocarpic fruit also had an increased pedicel length and fruit shape index and also showed a slight protrusion
of the calyx end. CPPU, GA4 and GA7 alone or combination with uniconazole were also active in inducing parthenogenesis in three other Rosaceae species, although
final fruit set was extremely low. GA1 was essentially inactive in promoting fruit expansion unlike the other bioactive GAs, whose effectiveness in promoting fruit
cell expansion was as follow: GA4 ≈ GA7 > GA3 > GA1. 相似文献
60.
Marcos Fernando Basso Karoline Estefani Duarte Thais Ribeiro Santiago Wagner Rodrigo de Souza Bruno de Oliveira Garcia Brbara Dias Brito da Cunha Adilson Kenji Kobayashi Hugo Bruno Correa Molinari 《Plant Biotechnology》2021,38(2):227
The CRISPR/Cas9 system has been used for genome editing in several organisms, including higher plants. This system induces site-specific mutations in the genome based on the nucleotide sequence of engineered guide RNAs. The complex genomes of C4 grasses makes genome editing a challenge in key grass crops like maize (Zea mays), sorghum (Sorghum bicolor), Brachiaria spp., switchgrass (Panicum virgatum), and sugarcane (Saccharum spp.). Setaria viridis is a diploid C4 grass widely used as a model for these C4 crop plants. Here, an optimized CRISPR/Cas9 binary vector that exploits the non-homologous end joining (NHEJ) system was used to knockout a green fluorescent protein (gfp) transgene in S. viridis accession A10.1. Transformation of embryogenic callus by A. tumefaciens generated ten glufosinate-ammonium resistant transgenic events. In the T0 generation, 60% of the events were biallelic mutants in the gfp transgene with no detectable accumulation of GFP protein and without insertions or deletions in predicted off-target sites. The gfp mutations generated by CRISPR/Cas9 were stable and displayed Mendelian segregation in the T1 generation. Altogether, the system described here is a highly efficient genome editing system for S. viridis, an important model plant for functional genomics studies in C4 grasses. Also, this system is a potential tool for improvement of agronomic traits in C4 crop plants with complex genomes. 相似文献