全文获取类型
收费全文 | 4135篇 |
免费 | 387篇 |
国内免费 | 241篇 |
出版年
2024年 | 3篇 |
2023年 | 38篇 |
2022年 | 117篇 |
2021年 | 211篇 |
2020年 | 123篇 |
2019年 | 162篇 |
2018年 | 178篇 |
2017年 | 130篇 |
2016年 | 174篇 |
2015年 | 288篇 |
2014年 | 287篇 |
2013年 | 345篇 |
2012年 | 363篇 |
2011年 | 349篇 |
2010年 | 208篇 |
2009年 | 175篇 |
2008年 | 237篇 |
2007年 | 195篇 |
2006年 | 152篇 |
2005年 | 160篇 |
2004年 | 114篇 |
2003年 | 119篇 |
2002年 | 88篇 |
2001年 | 84篇 |
2000年 | 69篇 |
1999年 | 69篇 |
1998年 | 42篇 |
1997年 | 38篇 |
1996年 | 37篇 |
1995年 | 38篇 |
1994年 | 27篇 |
1993年 | 20篇 |
1992年 | 24篇 |
1991年 | 24篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 11篇 |
1987年 | 12篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有4763条查询结果,搜索用时 546 毫秒
281.
282.
Chae PS Rasmussen SG Rana RR Gotfryd K Chandra R Goren MA Kruse AC Nurva S Loland CJ Pierre Y Drew D Popot JL Picot D Fox BG Guan L Gether U Byrne B Kobilka B Gellman SH 《Nature methods》2010,7(12):1003-1008
The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces of native IMPs. Many proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each built around a central quaternary carbon atom derived from neopentyl glycol, with hydrophilic groups derived from maltose. Representatives of this maltose-neopentyl glycol (MNG) amphiphile family show favorable behavior relative to conventional detergents, as manifested in multiple membrane protein systems, leading to enhanced structural stability and successful crystallization. MNG amphiphiles are promising tools for membrane protein science because of the ease with which they may be prepared and the facility with which their structures may be varied. 相似文献
283.
Gao J Luo J Li Y Fan R Zhao H Guan G Liu J Wiske B Sugimoto C Yin H 《Experimental & applied acarology》2007,41(4):289-303
A primary cDNA library with a size of 1.34 × 106 PFU was constructed from Haemaphysalis qinghaiensis eggs and was immunoscreened with rabbit anti-H. qinghaiensis serum. One clone (Hq22, named following those clones obtained from adult Haemaphysalis qinghaiensis cDNA library which we constructed before) screened from the cDNA library was selected randomly for sequencing. The entire
sequence of the clone was subsequently obtained using rapid amplification of the cDNA ends (RACE). A search of the cloned
sequence against GenBank revealed that it related to ribosomal protein L23a (Rpl23a) and had a high percentage similarity
to this protein from different species. Conserved domains for Rpl23a were also identified in the cloned sequence. Expression
analysis by RT-PCR showed that this gene is expressed in salivary glands, midguts, other tissues and different developmental
stages of H. qinghaiensis. Based on the H. qinghaiensis Rpl23a sequence, open reading frames (ORF) of Rpl23a of Heamaphysalis longicornis and Boophilus microplus were also cloned and were performed for comparison with Rpl23a of H. qinghaiensis and other organisms as well. Vaccine based on Rpl23a recombinant protein cannot protect sheep against H. qinghaiensis. 相似文献
284.
Shen J Wu Y Shi L Liu J Liu S Guan Z Yin Z 《Applied microbiology and biotechnology》2007,76(1):141-149
The extracellular portion (amino acids 95–281 or 114–281) of the human tumor necrosis factor-related apoptosis-inducing ligand
(sTRAIL) was genetically linked to the C terminus of the fluoresce-enhanced green fluorescent protein variant (EGFP) to generate
two versions of EGFP–sTRAIL fusion proteins, designated EGFP–sTR95 and EGFP–sTR114, respectively. The two versions of EGFP–sTRAIL
fusion proteins both induce extensive apoptosis in lymphoid as well as nonlymphoid tumor cell lines. In addition, the two
versions of fusion proteins retain similar fluorescence spectra to those of EGFP and have shown the specific binding to TRAIL
receptor-positive cells; thus, the stained cells could be analyzed with flow cytometry. Hence, the two versions of fusion
proteins represent a readily obtainable source of biologically active sTRAIL that may prove useful in exploit fully the characteristics
of both the soluble TRAIL and its receptor system. 相似文献
285.
286.
287.
Bnip3 mediates the hypoxia-induced inhibition on mammalian target of rapamycin by interacting with Rheb 总被引:1,自引:0,他引:1
Li Y Wang Y Kim E Beemiller P Wang CY Swanson J You M Guan KL 《The Journal of biological chemistry》2007,282(49):35803-35813
The mammalian target of rapamycin (mTOR) is a central controller of cell growth, and it regulates translation, cell size, cell viability, and cell morphology. mTOR integrates a wide range of extracellular and intracellular signals, including growth factors, nutrients, energy levels, and stress conditions. Rheb, a Ras-related small GTPase, is a key upstream activator of mTOR. In this study, we found that Bnip3, a hypoxia-inducible Bcl-2 homology 3 domain-containing protein, directly binds Rheb and inhibits the mTOR pathway. Bnip3 decreases Rheb GTP levels in a manner depending on the binding to Rheb and the presence of the N-terminal domain. Both knockdown and overexpression experiments show that Bnip3 plays an important role in mTOR inactivation in response to hypoxia. Moreover, Bnip3 inhibits cell growth in vivo by suppressing the mTOR pathway. These observations demonstrate that Bnip3 mediates the inhibition of the mTOR pathway in response to hypoxia. 相似文献
288.
Guan Y Yoganandan N Moore J Pintar FA Zhang J Maiman DJ Laud P 《Journal of biomechanics》2007,40(9):1975-1980
The objective of this study was to test the hypothesis that the human lumbosacral joint behaves differently from L1-L5 joints and provides primary moment-rotation responses under pure moment flexion and extension and left and right lateral bending on a level-by-level basis. In addition, range of motion (ROM) and stiffness data were extracted from the moment-rotation responses. Ten T12-S1 column specimens with ages ranging from 27 to 68 years (mean: 50.6+/-13.2) were tested at a load level of 4.0 N m. Nonlinear flexion and extension and left and right lateral bending moment-rotation responses at each spinal level are reported in the form of a logarithmic function. The mean ROM was the greatest at the L5-S1 level under flexion (7.37+/-3.69 degrees) and extension (4.62+/-2.56 degrees) and at the L3-L4 level under lateral bending (4.04+/-1.11 degrees). The mean ROM was the least at the L1-L2 level under flexion (2.42+/-0.90 degrees), L2-L3 level under extension (1.58+/-0.63 degrees), and L1-L2 level under lateral bending (2.50+/-0.75 degrees). The present study proved the hypothesis that L5-S1 motions are significantly greater than L1-L5 motions under flexion and extension loadings, but the hypothesis was found to be untrue under the lateral bending mode. These experimental data are useful in the improved validation of FE models, which will increase the confidence of stress analysis and other modeling applications. 相似文献
289.
Establishment of influenza A virus (H6N1) in minor poultry species in southern China 总被引:4,自引:1,他引:3
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cheung CL Vijaykrishna D Smith GJ Fan XH Zhang JX Bahl J Duan L Huang K Tai H Wang J Poon LL Peiris JS Chen H Guan Y 《Journal of virology》2007,81(19):10402-10412
An H6N1 virus, A/teal/Hong Kong/W312/97 (W312), was isolated during the "bird flu" incident in Hong Kong in 1997. Genetic analysis suggested that this virus might be the progenitor of the A/Hong Kong/156/97 (HK/97) H5N1 virus, as seven of eight gene segments of those viruses had a common source. Continuing surveillance in Hong Kong showed that a W312-like virus was prevalent in quail and pheasants in 1999; however, the further development of H6N1 viruses has not been investigated since 2001. Here we report influenza virus surveillance data collected in southern China from 2000 to 2005 that show that H6N1 viruses have become established and endemic in minor poultry species and replicate mainly in the respiratory tract. Phylogenetic analysis indicated that all H6N1 isolates had W312-like hemagglutinin and neuraminidase genes. However, reassortment of internal genes between different subtype virus lineages, including H5N1, H9N2, and other avian viruses, generated multiple novel H6N1 genotypes in different types of poultry. These novel H6N1/N2 viruses are double, triple, or even quadruple reassortants. Reassortment between a W312-like H6N1 virus and an A/quail/Hong Kong/G1/97 (HK/97)-like H9N2 virus simultaneously generated novel H6N2 subtype viruses that were persistent in poultry. Molecular analyses suggest that W312-like viruses may not be the precursors of HK/97 virus but reassortants from an HK/97-like virus and another unidentified H6 subtype virus. These results provide further evidence of the pivotal role of the live poultry market system of southern China in generating increased genetic diversity in influenza viruses in this region. 相似文献
290.
Lee CH Inoki K Karbowniczek M Petroulakis E Sonenberg N Henske EP Guan KL 《The EMBO journal》2007,26(23):4812-4823
Miscoordination of growth and proliferation with the cellular stress response can lead to tumorigenesis. Mammalian target of rapamycin (mTOR), a central cell growth controller, is highly activated in some malignant neoplasms, and its clinical implications are under extensive investigation. We show that constitutive mTOR activity amplifies p53 activation, in vitro and in vivo, by stimulating p53 translation. Thus, loss of TSC1 or TSC2, the negative regulators of mTOR, results in dramatic accumulation of p53 and apoptosis in response to stress conditions. In other words, the inactivation of mTOR prevents cell death by nutrient stress and genomic damage via p53. Consistently, we also show that p53 is elevated in TSC tumors, which rarely become malignant. The coordinated relationship between mTOR and p53 during cellular stress provides a possible explanation for the benign nature of hamartoma syndromes, including TSC. Clinically, this also suggests that the efficacy of mTOR inhibitors in anti-neoplastic therapy may also depend on p53 status, and mTOR inhibitors may antagonize the effects of genotoxic chemotherapeutics. 相似文献