全文获取类型
收费全文 | 10050篇 |
免费 | 833篇 |
国内免费 | 875篇 |
专业分类
11758篇 |
出版年
2024年 | 25篇 |
2023年 | 167篇 |
2022年 | 343篇 |
2021年 | 572篇 |
2020年 | 409篇 |
2019年 | 454篇 |
2018年 | 448篇 |
2017年 | 294篇 |
2016年 | 430篇 |
2015年 | 667篇 |
2014年 | 747篇 |
2013年 | 782篇 |
2012年 | 894篇 |
2011年 | 768篇 |
2010年 | 523篇 |
2009年 | 424篇 |
2008年 | 533篇 |
2007年 | 462篇 |
2006年 | 408篇 |
2005年 | 326篇 |
2004年 | 271篇 |
2003年 | 252篇 |
2002年 | 189篇 |
2001年 | 173篇 |
2000年 | 151篇 |
1999年 | 167篇 |
1998年 | 91篇 |
1997年 | 83篇 |
1996年 | 76篇 |
1995年 | 74篇 |
1994年 | 95篇 |
1993年 | 48篇 |
1992年 | 52篇 |
1991年 | 67篇 |
1990年 | 42篇 |
1989年 | 48篇 |
1988年 | 32篇 |
1987年 | 26篇 |
1986年 | 34篇 |
1985年 | 25篇 |
1984年 | 16篇 |
1983年 | 12篇 |
1982年 | 10篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1978年 | 4篇 |
1973年 | 4篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1968年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 8 毫秒
1.
Structural Insight of a Trimodular Halophilic Cellulase with a Family 46 Carbohydrate-Binding Module
Huaidong Zhang Guimin Zhang Chaoxiang Yao Muhammad Junaid Zhenghui Lu Houjin Zhang Yanhe Ma 《PloS one》2015,10(11)
Cellulases are the key enzymes used in the biofuel industry. A typical cellulase contains a catalytic domain connected to a carbohydrate-binding module (CBM) through a flexible linker. Here we report the structure of an atypical trimodular cellulase which harbors a catalytic domain, a CBM46 domain and a rigid CBM_X domain between them. The catalytic domain shows the features of GH5 family, while the CBM46 domain has a sandwich-like structure. The catalytic domain and the CBM46 domain form an extended substrate binding cleft, within which several tryptophan residues are well exposed. Mutagenesis assays indicate that these residues are essential for the enzymatic activities. Gel affinity electrophoresis shows that these tryptophan residues are involved in the polysaccharide substrate binding. Also, electrostatic potential analysis indicates that almost the entire solvent accessible surface of CelB is negatively charged, which is consistent with the halophilic nature of this enzyme. 相似文献
2.
Jian Xiao Dan Chen Xiu-Xian Lin Shi-Fang Peng Mei-Fang Xiao Wei-Hua Huang Yi-Cheng Wang Jing-Bo Peng Wei Zhang Dong-Sheng Ouyang Yao Chen 《PloS one》2016,11(2)
Ginsenoside compound K (CK), a rare ginsenoside originating from Panax Ginseng, has been found to possess unique pharmacological activities specifically as anti-cancers. However, the role of cytochrome P450s (CYPs) in the metabolism of CK is unclear. In this study, we screened the CYPs for the metabolism of CK in vitro using human liver microsomes (HLMs) or human recombinant CYPs. The results showed that CK inhibited the enzyme activities of CYP2C9 and CYP3A4 in the HLMs. The Km and Vmax values of CK were 84.20±21.92 μM and 0.28±0.04 nmol/mg protein/min, respectively, for the HLMs; 34.63±10.48 μM and 0.45±0.05 nmol/nmol P450/min, respectively, for CYP2C9; and 27.03±5.04 μM and 0.68±0.04 nmol/nmol P450/min, respectively, for CYP3A4. The IC50 values were 16.00 μM and 9.83 μM, and Ki values were 14.92 μM and 11.42μM for CYP2C9 and CYP3A4, respectively. Other human CYP isoforms, including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on CK metabolism. The results suggested that CK was a substrate and also inhibitors for both CYP2C9 and CYP3A4. Patients using CK in combination with therapeutic drugs that are substrates of CYP2C9 and CYP3A4 for different reasons should be careful, although the inhibiting potency of CK is much poorer than that of enzyme-specific inhibitors. 相似文献
3.
4.
5.
Wenjun Geng Jinggong Xiangyu Xiuzhen Li Zhongning Zhang Deyuan Han Yongwei Li 《Insect Science》1997,4(4):364-368
Abstract Field trials by sex pheromone of aphid to trap peach aphids Myzus persicae have been carried out in 1995 and in 1996. Suitable time and the effect of ratio of two components nepetalactone and nepetalactol to apply the lure have been observed. 相似文献
6.
Y. Saijo S. Takeda A. Scherer T. Kobayashi Y. Mada H. Taniguchi M. Yao S. Wakatsuki 《Protein science : a publication of the Protein Society》1997,6(4):916-918
Troponin is a ternary protein complex consisting of subunits TnC. TnI, and TnT, and plays a key role in calcium regulation of the skeletal and cardiac muscle contraction. In the present study, a partial complex (CI47) was prepared from Escherichia coli-expressed rabbit skeletal muscle TnC and fragment 1-47 of TnI, which is obtained by chemical cleavage of an E. coli-expressed mutant of rabbit skeletal muscle TnI. Within the ternary troponin complex, CI47 is thought to form a core that is resistant to proteolytic digestion, and the interaction within CI47 likely maintains the integrity of the troponin complex. Complex CI47 was crystallized in the presence of sodium citrate. The addition of trehalose improved the diffraction pattern of the crystals substantially. The crystal lattice belongs to the space group P3(1)(2)21, with unit cell dimensions a = b = 48.2 A, c = 162 A. The asymmetric unit presumably contains one CI47 complex. Soaking with p-chloromercuribenzenesulfonate (PCMBS) resulted in loss of isomorphism, but enhanced the quality of the crystals. The crystals diffracted up to 2.3 A resolution, with completeness of 91% and R(merge) = 6.4%. The crystals of PCMBS-derivative should be suitable for X-ray studies using the multiple-wavelength anomalous diffraction technique. This is the first step for elucidating the structure of the full troponin complex. 相似文献
7.
Tristan J. Iseli Nigel Turner Xiao-Yi Zeng Gregory J. Cooney Edward W. Kraegen Sheng Yao Yang Ye David E. James Ji-Ming Ye 《PloS one》2013,8(4)
We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKKβ inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK. 相似文献
8.
Hiroshi Yao Hiroaki Ooboshi Seizo Sadoshima Kentaro Takano Setsuro Ibayashi Masatoshi Fujishima 《Neurochemical research》1990,15(5):547-549
To determine the level of cerebral blood flow reduction which causes striatal dopamine release, extracellular dopamine and cerebral blood flow was simultaneously determined using in vivo brain dialysis and a hydrogen clearance method, respectively, in the striatum of spontaneously hypertensive rats, before and during experimental cerebral ischemia. The ischemic flow threshold for neurotransmitter dopamine release was found to be 20% of the resting value or 8–10 ml/100g/min of cerebral blood flow, being similar to those for energy and membrane failures. 相似文献
9.
Tatsuo Nakahara Makoto Hirano Takashi Matsumoto Toshihide Kuroki Yoshinori Tatebayashi Tetsuyuki Tsutsumi Kouji Nishiyama Hiroaki Ooboshi Kaoru Nakamura Hiroshi Yao Akio Shiraishi Michinori Waki Hideyuki Uchimura 《Neurochemical research》1990,15(6):609-611
DNA and RNA contents in 20 brain regions or nuclei of the rat were determined by a highly sensitive method using high-performance liquid chromatography with electrochemical detection. The high DNA and RNA contents were found in the hypothalamic nuclei, especially the median eminence-arcuate nucleus. These results may be available for the preparation of nucleic acids as the regional control. 相似文献
10.
Transformation of Tetrahymena thermophila with hypermethylated rRNA genes. 总被引:5,自引:3,他引:2 下载免费PDF全文
The extrachromosomal rRNA genes (rDNA) of Tetrahymena thermophila contain 0.4% N6-methyladenine. C3 strain rDNA was isolated, hypermethylated in vitro, and microinjected into B strain host cells. Clonal cell lines were established, and transformants were selected on the basis of resistance to paromomycin, conferred by the injected rDNA. The effects of methylation by three enzymes which methylate the sequence 5'-NAT-3', the dam, EcoRI, and ClaI methylases, were tested. Hypermethylation of the injected rDNA had no effect on transformation efficiency relative to mock-methylated controls. The injected C3 strain rDNA efficiently replaced host rDNA as the major constituent of the population of rDNA molecules. Hypermethylation of the injected DNA was not maintained through 20 to 25 cell generations. 相似文献