全文获取类型
收费全文 | 1675篇 |
免费 | 76篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 16篇 |
2022年 | 30篇 |
2021年 | 52篇 |
2020年 | 32篇 |
2019年 | 35篇 |
2018年 | 53篇 |
2017年 | 34篇 |
2016年 | 78篇 |
2015年 | 78篇 |
2014年 | 101篇 |
2013年 | 137篇 |
2012年 | 178篇 |
2011年 | 162篇 |
2010年 | 80篇 |
2009年 | 93篇 |
2008年 | 98篇 |
2007年 | 97篇 |
2006年 | 92篇 |
2005年 | 67篇 |
2004年 | 68篇 |
2003年 | 52篇 |
2002年 | 33篇 |
2001年 | 13篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 8篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1978年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有1752条查询结果,搜索用时 15 毫秒
11.
12.
Extensively drug-resistant tuberculosis (XDR-TB) is defined as tuberculosis caused by a Mycobacterium tuberculosis strain that is resistant to at least rifampicin and isoniazid among the first-line antitubercular drugs (multidrug-resistant tuberculosis; MDR-TB) in addition to resistance to any fluroquinolones and at least one of three injectable second-line drugs, namely amikacin, kanamycin and/or capreomycin. Recent studies have described XDR-TB strains from all continents. Worldwide prevalence of XDR-TB is estimated to be c. 6.6% in all the studied countries among multidrug-resistant M. tuberculosis strains. The emergence of XDR-TB strains is a reflection of poor tuberculosis management, and controlling its emergence constitutes an urgent global health reality and a challenge to tuberculosis control activities in all parts of the world, especially in developing countries and those lacking resources and as well as in countries with increasing prevalence of HIV/AIDS. 相似文献
13.
Swagata Ghatak Dorit Trudler Nima Dolatabadi Rajesh Ambasudhan 《Journal of genetics》2018,97(3):729-751
Parkinson’s disease (PD) is a debilitating neurodegenerative disorder, for which people above the age of 60 show an increased risk. Although there has been great advancement in understanding the disease-related abnormalities in brain circuitry and development of symptomatic treatments, a cure for PD remains elusive. The discovery of PD associated gene mutations and environmental toxins have yielded animal models of the disease. These models could recapitulate several key aspects of PD, and provide more insights into the disease pathogenesis. They have also revealed novel aspects of the disease mechanism including noncell autonomous events and spreading of pathogenic protein species across the brain. Nevertheless, none of these models so far can comprehensively represent all aspects of the human disease. While the field is still searching for the perfect model system, recent developments in stem cell biology have provided a new dimension to modelling PD, especially doing it in a patient-specific manner. In the current review, we attempt to summarize the key findings in the areas discussed above, and highlight how the core PD pathology distinguishes itself from other neurodegenerative disorders while also resembling them in many aspects. 相似文献
14.
This proof-of-concept study explores the feasibility of using a drug-loaded hydrophilic polymeric layer sandwiched between two hydrophobic layers for improving film drug load while achieving sustained release of poorly water-soluble drug. Such films having total thickness in range ~?146–250 μm were prepared by slurry-based casting using hydrophilic hydroxypropyl methylcellulose (HPMC) as matrix layer containing fenofibrate (FNB) as the model drug, encased between two very thin rate-limiting layers of 10 μm each of hydrophobic poly-?-caprolactone (PCL). Film precursor slurry consisted of HPMC with plasticizer and water along with micronized FNB powders, which were dry-coated with hydrophilic silica. Characterization techniques demonstrated the presence of homogeneously dispersed crystalline FNB in films. The films are very thin and hence two-dimensional; hence, average drug load per unit area in range ~?5 to ~?9 mg/cm2 could be achieved by altering the thickness of the drug matrix layer. Drug amount and drug content uniformity were measured through assay of ten circular samples ~?0.712 cm2 in area punched out using a circular-shaped punch tool. Drug release rate was investigated using USP IV flow-through cell and surface dissolution imaging system. Thinner films followed Fickian diffusion, and thicker films followed non-Fickian anomalous diffusion. Overall, the application of middle layer thickness could be used as a tool to manipulate drug load without the need for altering its formulation or precursor preparation by changing its thickness, hence achieving relatively high drug loading yet having sustained release of drug. 相似文献
15.
16.
Centrioles are self-reproducing organelles that form the core structure of centrosomes or microtubule-organizing centers (MTOCs). However, whether duplication and MTOC organization reflect innate activities of centrioles or activities acquired conditionally is unclear. In this paper, we show that newly formed full-length centrioles had no inherent capacity to duplicate or to organize pericentriolar material (PCM) but acquired both after mitosis through a Plk1-dependent modification that occurred in early mitosis. Modified centrioles initiated PCM recruitment in G1 and segregated equally in mitosis through association with spindle poles. Conversely, unmodified centrioles segregated randomly unless passively tethered to modified centrioles. Strikingly, duplication occurred only in centrioles that were both modified and disengaged, whereas unmodified centrioles, engaged or not, were "infertile," indicating that engagement specifically blocks modified centrioles from reduplication. These two requirements, centriole modification and disengagement, fully exclude unlimited duplication in one cell cycle. We thus uncovered a Plk1-dependent mechanism whereby duplication and segregation are coupled to maintain centriole homeostasis. 相似文献
17.
Fluorescence resonance energy transfer (FRET) microscopy imaging of live cell protein localizations 总被引:13,自引:0,他引:13
The current advances in fluorescence microscopy, coupled with the development of new fluorescent probes, make fluorescence resonance energy transfer (FRET) a powerful technique for studying molecular interactions inside living cells with improved spatial (angstrom) and temporal (nanosecond) resolution, distance range, and sensitivity and a broader range of biological applications. 相似文献
18.
T. Rajesh S. Maruthasalam K. Kalpana K. Poovannan K. K. Kumar E. Kokiladevi D. Sudhakar R. Samiyappan P. Balasubramanian 《Biologia Plantarum》2016,60(4):749-756
Development of transgenic plants by introducing defense genes is one of the strategies to engineer disease resistance. Transgenic ASD16 rice plants harbouring rice chitinase chi11 gene, belonging to a PR-3 group of defense gene conferring sheath blight (Rhizoctonia solani Kuhn) resistance, were used in this study. Three T2 homozygous lines (ASD16-4-1-1, 5-1-1, and 6-1-1) were identified from seven putative (T0) transgenic lines expressing chi11 using Western blotting analysis. The inheritance of sheath blight resistance in those lines was studied over generations. The stability of chi11 expression up to T4 generation in all the three homozygous lines was proved by Western blot and the stability of sheath blight resistance in the homozygous lines was proved up to T4 generation using detached leaf and intact leaf sheath assays. Among the three homozygous lines tested, ASD16-4-1-1 showed consistent results in all the generations and gave a better protection against the sheath blight pathogen than the other two lines. 相似文献
19.
David B. Kantor Cameron D. Palmer Taylor R. Young Yan Meng Zofia K. Gajdos Helen Lyon Alkes L. Price Samuela Pollack Stephanie J. London Laura R. Loehr Lewis J. Smith Rajesh Kumar David R. Jacobs Jr. Marcy F. Petrini George T. O’Connor Wendy B. White George Papanicolaou Kristin M. Burkart Susan R. Heckbert R. Graham Barr Joel N. Hirschhorn 《Human genetics》2013,132(9):1039-1047
Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry. 相似文献
20.
Amod M. Zambre Akshay Khandekar Rajesh Sanap Clairissa O'Brien Emilie C. Snell-Rood Maria Thaker 《Proceedings. Biological sciences / The Royal Society》2020,287(1940)
Interspecific competition can occur when species are unable to distinguish between conspecific and heterospecific mates or competitors when they occur in sympatry. Selection in response to interspecific competition can lead to shifts in signalling traits—a process called agonistic character displacement. In two fan-throated lizard species—Sitana laticeps and Sarada darwini—females are morphologically indistinguishable and male agonistic signalling behaviour is similar. Consequently, in areas where these species overlap, males engage in interspecific aggressive interactions. To test whether interspecific male aggression between Si. laticeps and Sa. darwini results in agonistic character displacement, we quantified species recognition and signalling behaviour using staged encounter assays with both conspecifics and heterospecifics across sympatric and allopatric populations of both species. We found an asymmetric pattern, wherein males of Si. laticeps but not Sa. darwini showed differences in competitor recognition and agonistic signalling traits (morphology and behaviour) in sympatry compared with allopatry. This asymmetric shift in traits is probably due to differences in competitive abilities between species and can minimize competitive interactions in zones of sympatry. Overall, our results support agonistic character displacement, and highlight the role of asymmetric interspecific competition in driving shifts in social signals. 相似文献