全文获取类型
收费全文 | 1668篇 |
免费 | 145篇 |
国内免费 | 68篇 |
专业分类
1881篇 |
出版年
2023年 | 14篇 |
2022年 | 37篇 |
2021年 | 51篇 |
2020年 | 23篇 |
2019年 | 41篇 |
2018年 | 36篇 |
2017年 | 41篇 |
2016年 | 56篇 |
2015年 | 67篇 |
2014年 | 84篇 |
2013年 | 85篇 |
2012年 | 110篇 |
2011年 | 102篇 |
2010年 | 80篇 |
2009年 | 65篇 |
2008年 | 76篇 |
2007年 | 88篇 |
2006年 | 83篇 |
2005年 | 62篇 |
2004年 | 49篇 |
2003年 | 52篇 |
2002年 | 55篇 |
2001年 | 28篇 |
2000年 | 29篇 |
1999年 | 30篇 |
1998年 | 15篇 |
1997年 | 16篇 |
1996年 | 13篇 |
1995年 | 12篇 |
1994年 | 15篇 |
1993年 | 12篇 |
1992年 | 25篇 |
1991年 | 22篇 |
1990年 | 22篇 |
1989年 | 30篇 |
1988年 | 29篇 |
1987年 | 17篇 |
1986年 | 15篇 |
1985年 | 13篇 |
1984年 | 18篇 |
1983年 | 12篇 |
1982年 | 11篇 |
1981年 | 9篇 |
1980年 | 8篇 |
1979年 | 10篇 |
1978年 | 7篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1973年 | 7篇 |
1911年 | 7篇 |
排序方式: 共有1881条查询结果,搜索用时 15 毫秒
61.
62.
Genome editing with engineered nucleases (GEEN) represents a highly specific and efficient tool for crop improvement with the potential to rapidly generate useful novel phenotypes/traits. Genome editing techniques initiate specifically targeted double strand breaks facilitating DNA‐repair pathways that lead to base additions or deletions by non‐homologous end joining as well as targeted gene replacements or transgene insertions involving homology‐directed repair mechanisms. Many of these techniques and the ancillary processes they employ generate phenotypic variation that is indistinguishable from that obtained through natural means or conventional mutagenesis; and therefore, they do not readily fit current definitions of genetically engineered or genetically modified used within most regulatory regimes. Addressing ambiguities regarding the regulatory status of genome editing techniques is critical to their application for development of economically useful crop traits. Continued regulatory focus on the process used, rather than the nature of the novel phenotype developed, results in confusion on the part of regulators, product developers, and the public alike and creates uncertainty as of the use of genome engineering tools for crop improvement. 相似文献
63.
64.
Stefan Petrasch Steven J. Knapp Jan A. L. van Kan Barbara Blanco-Ulate 《Molecular Plant Pathology》2019,20(6):877-892
The fungal pathogen Botrytis cinerea causes grey mould, a commercially damaging disease of strawberry. This pathogen affects fruit in the field, storage, transport and market. The presence of grey mould is the most common reason for fruit rejection by growers, shippers and consumers, leading to significant economic losses. Here, we review the biology and epidemiology of the pathogen, mechanisms of infection and the genetics of host plant resistance. The development of grey mould is affected by environmental and genetic factors; however, little is known about how B. cinerea and strawberry interact at the molecular level. Despite intensive efforts, breeding strawberry for resistance to grey mould has not been successful, and the mechanisms underlying tolerance to B. cinerea are poorly understood and under-investigated. Current control strategies against grey mould include pre- and postharvest fungicides, yet they are generally ineffective and expensive. In this review, we examine available research on horticultural management, chemical and biological control of the pathogen in the field and postharvest storage, and discuss their relevance for integrative disease management. Additionally, we identify and propose approaches for increasing resistance to B. cinerea in strawberry by tapping into natural genetic variation and manipulating host factors via genetic engineering and genome editing. 相似文献
65.
Janina V. Pearce Jared S. Farrar Joseph C. Lownik Bin Ni Shanshan Chen Tiffany W. Kan Francesco S. Celi 《Biochemistry and Biophysics Reports》2019
Breast cancer remains a substantial clinical problem worldwide, and cancer-associated cachexia is a condition associated with poor prognosis in this and other malignancies. Adipose tissue is involved in the development and progression of cancer-associated cachexia, but its various roles and mechanisms of action are not completely defined, especially as it relates to breast cancer. Interleukin 6 has been implicated in several mechanisms contributing to increased breast cancer tumorigenesis, as well as a net-negative energy balance and cancer-associated cachexia via adipose tissue remodeling in other models of cancer; however, its potential role in breast cancer-associated white adipose browning has not been explored. In this study, we demonstrate localized white adipose tissue browning in a spontaneous model of murine mammary cancer. We then used an in vitro murine adipocyte culture system with the E0771 and 4T1 cell lines as models of breast cancer. We demonstrate that while the E0771 and 4T1 secretomes and cross-talk with white adipocytes alter white adipocyte mRNA expression, they do not directly induce white adipocyte browning. Additionally, we show that neither exogenous administration of interleukin 6 alone or with its soluble receptor directly induce white adipocyte browning. Together, these results demonstrate that neither the E0771 or 4T1 murine breast cancer cell lines, nor interleukin 6, directly cause browning of cultured white adipocytes. This suggests that their roles in adipose tissue remodeling are more complex and indirect in nature. 相似文献
66.
Structural characterization and immunological activity of two cold-water extractable polysaccharides from Cistanche deserticola Y. C. Ma 总被引:1,自引:0,他引:1
Two major polysaccharide fractions, CDA-1A and CDA-3B, were isolated from the cold-water extract of Cistanche deserticola Y. C. Ma, a holoparasitic plant and a valuable traditional Chinese medicine, using anion-exchange chromatography on DEAE-cellulose and gel-permeation chromatography on Sephacryl S-300 and Sephadex G-150. Their major structural features were elucidated using component and linkage analyses, periodate oxidation, Smith degradation, partial acid hydrolysis, and NMR spectroscopy. The results indicated that CDA-1A is an alpha-(1-->4)-D-glucan with alpha-(1-->6)-linked branches attached to the O-6 of branch points and that CDA-3B is an RG-I polysaccharide containing a typical rhamnogalacturonan backbone and arabinogalactan or arabinan branches. Bioactivity tests showed that CDA-1A is inert for T-cell proliferation stimulation but active for B-cell proliferation, while CDA-3B is potent for the stimulation of both T- and B-cell proliferation. 相似文献
67.
68.
Jean-Yu Hwang Wei-Chih Kan Yao-Bin Liu Lea-Yea Chuang Jinn-Yuh Guh Yu-Lin Yang Jau-Shyang Huang 《Journal of cellular physiology》2019,234(10):17473-17481
Advanced glycation end products (AGE) and angiotensin II were closely correlated with the progression of diabetic nephopathy (DN). Nitric oxide (NO) is a protective mediator of renal tubular hypertrophy in DN. Here, we examined the molecular mechanisms of angiotensin-converting enzyme inhibitor (ACEI) and NO signaling responsible for diminishing AGE-induced renal tubular hypertrophy. In human renal proximal tubular cells, AGE decreased NO production, inducible NOS activity, guanosine 3′,5′-cyclic monophosphate (cGMP) synthesis, and cGMP-dependent protein kinase (PKG) activation. All theses effects of AGE were reversed by treatment with ACEIs (captopril and enalapril), the NO donor S-nitroso-N-acetylpenicillamine (SNAP), and the PKG activator 8-para-chlorophenylthio-cGMPs (8-pCPT-cGMPs). In addition, AGE-enhanced activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) were clearly reduced by captopril, enalapril, SNAP, and 8-pCPT-cGMPs. The abilities of ACEIs and NO/PKG activation to inhibit AGE-induced hypertrophic growth were verified by the observation that captopril, enalapril, SNAP, and 8-pCPT-cGMPs decreased protein levels of fibronectin, p21 Waf1/Cip1, and receptor for AGE. The results of the present study suggest that ACEIs significantly reduced AGE-increased ERK/JNK/p38 MAPK activation and renal tubular hypertrophy partly through enhancement of the NO/PKG pathway. 相似文献
69.
Wenhua Xue Zhirui Fan Lifeng Li Dan Yan Zhibo Shen Yunkai Zhai Quancheng Kan Jie Zhao 《Journal of cellular physiology》2019,234(10):18098-18110
The purpose of this study is to better understand the role of interleukin 35 (IL35) in esophageal carcinoma by comparing the mRNA level in Barrett's esophageal mucosa and in matched normal squamous mucosa and to understand how the diagnosis model works with two other genes: hepatocyte nuclear factor 1B (HNF1B) and cAMP responsive element binding protein 3-like 1 (CREB3L1). By comparing carcinoma tissue and normal tissue samples, we extracted all the differentially expressed mRNAs. The bioinformatics analysis resulted in the discovery of three prominent genes. Eventually, the three genes were utilized to train a deep-learning model. An additional wet experiment was conducted to validate the effect of IL35. All the differentially expressed genes were enriched into nine groups, each of which has specific biological functions. Given that the three significant genes HNF1B, CREB3L1, and IL35 as diagnostic features, a deep-learning model was constructed, reaching an accuracy of 93% in the training set and 87% in the test set. Our findings suggest that IL35, along with the other two signatures, can distinguish esophageal tumor samples from normal samples precisely. 相似文献
70.
Eiichiro Kan Yohei Katsuyama Jun-ichi Maruyama Koichi Tamano Yasuji Koyama 《Bioscience, biotechnology, and biochemistry》2019,83(7):1372-1381
The filamentous fungus Aspergillus oryzae was recently used as a heterologous host for fungal secondary metabolite production. Here, we aimed to produce the plant polyketide curcumin in A. oryzae. Curcumin is synthesized from feruloyl-coenzyme A (CoA) and malonyl-CoA by curcuminoid synthase (CUS). A. oryzae expressing CUS produced curcumin (64 μg/plate) on an agar medium containing feruloyl-N-acetylcysteamine (a feruloyl-CoA analog). To increase curcumin yield, we attempted to strengthen the supply of malonyl-CoA using two approaches: enhancement of the reaction catalyzed by acetyl-CoA carboxylase (ACC), which produces malonyl-CoA from acetyl-CoA, and inactivation of the acetyl-CoA-consuming sterol biosynthesis pathway. Finally, we succeeded in increasing curcumin yield sixfold by the double disruption of snfA and SCAP; SnfA is a homolog of SNF1, which inhibits ACC activity by phosphorylation in Saccharomyces cerevisiae and SCAP is positively related to sterol biosynthesis in Aspergillus terreus. This study provided useful information for heterologous polyketide production in A. oryzae. 相似文献