全文获取类型
收费全文 | 1670篇 |
免费 | 82篇 |
国内免费 | 3篇 |
出版年
2023年 | 8篇 |
2022年 | 24篇 |
2021年 | 58篇 |
2020年 | 29篇 |
2019年 | 41篇 |
2018年 | 40篇 |
2017年 | 46篇 |
2016年 | 63篇 |
2015年 | 72篇 |
2014年 | 102篇 |
2013年 | 128篇 |
2012年 | 137篇 |
2011年 | 137篇 |
2010年 | 121篇 |
2009年 | 73篇 |
2008年 | 67篇 |
2007年 | 62篇 |
2006年 | 70篇 |
2005年 | 48篇 |
2004年 | 26篇 |
2003年 | 21篇 |
2002年 | 18篇 |
2001年 | 25篇 |
2000年 | 20篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 13篇 |
1996年 | 11篇 |
1995年 | 6篇 |
1994年 | 10篇 |
1993年 | 6篇 |
1991年 | 14篇 |
1990年 | 11篇 |
1989年 | 19篇 |
1988年 | 12篇 |
1987年 | 17篇 |
1986年 | 13篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 14篇 |
1980年 | 11篇 |
1979年 | 10篇 |
1977年 | 6篇 |
1974年 | 10篇 |
1973年 | 6篇 |
1969年 | 5篇 |
1968年 | 5篇 |
1967年 | 11篇 |
排序方式: 共有1755条查询结果,搜索用时 15 毫秒
41.
S. Raić M. Pongraćić J. Vorkapić-Furać D. Vikić-Topić A. Hergold-Brundić A. Nagl 《Nucleosides, nucleotides & nucleic acids》2013,32(4):937-960
Abstract Synthesis of the novel nucleoside analogues containing exocyclic pyrrolo moiety and acyclic side chains attached to the purine ring at N-9 and N-7 is described. The site of alkylation was determined by 1H and 13C NMR on the basis of chemical shifts, C-H coupling constants and connectivity in NOESY and HETCOR spectra. The N-9 substitution of 7 was proved by its X-ray crystallographic analysis. 相似文献
42.
Minakshi Mazumdar Arghya Adhikary Samik Chakraborty Shravanti Mukherjee Argha Manna Shilpi Saha Suchismita Mohanty Amrita Dutta Pushpak Bhattacharjee Pallab Ray Sreya Chattopadhyay Shuvomoy Banerjee Juni Chakraborty Arun K. Ray Gaurisankar Sa Tanya Das 《Apoptosis : an international journal on programmed cell death》2013,18(5):589-604
Mutations in REarranged during Transfection (RET) receptor tyrosine, followed by the oncogenic activation of RET kinase is responsible for the development of medullary thyroid carcinoma (MTC) that responds poorly to conventional chemotherapy. Targeting RET, therefore, might be useful in tailoring surveillance of MTC patients. Here we showed that theaflavins, the bioactive components of black tea, successfully induced apoptosis in human MTC cell line, TT, by inversely modulating two molecular pathways: (i) stalling PI3K/Akt/Bad pathway that resulted in mitochondrial transmembrane potential (MTP) loss, cytochrome-c release and activation of the executioner caspases-9 and -3, and (ii) upholding p38MAPK/caspase-8/caspase-3 pathway via inhibition of Ras/Raf/ERK. Over-expression of either constitutively active myristoylated-Akt-cDNA (Myr-Akt-cDNA) or dominant-negative-caspase-8-cDNA (Dn-caspase-8-cDNA) partially blocked theaflavin-induced apoptosis, while co-transfection of Myr-Akt-cDNA and Dn-caspase-8-cDNA completely eradicated the effect of theaflavins thereby negating the possibility of existence of other pathways. A search for the upstream signaling revealed that theaflavin-induced disruption of lipid raft caused interference in anchorage of RET in lipid raft that in turn stalled phosphorylation of Ras and PI3Kinase. In such anti-survival cellular micro-environment, pro-apoptotic signals were triggered to culminate into programmed death of MTC cell. These findings not only unveil a hitherto unexplained mechanism underlying theaflavin-induced MTC death, but also validate RET as a promising and potential target for MTC therapy. 相似文献
43.
Wayne Reeve Rui Tian Sofie De Meyer Vanessa Melino Jason Terpolilli Julie Ardley Ravi Tiwari John Howieson Ronald Yates Graham O’Hara Mohamed Ninawi Hazuki Teshima David Bruce Chris Detter Roxanne Tapia Cliff Han Chia-Lin Wei Marcel Huntemann James Han I-Min Chen Konstantinos Mavromatis Victor Markowitz Natalia Ivanova Galina Ovchinnikova Ioanna Pagani Amrita Pati Lynne Goodwin Sam Pitluck Tanja Woyke Nikos Kyrpides 《Standards in genomic sciences》2013,9(2):243-253
Rhizobium leguminosarum bv. trifolii strain TA1 is an aerobic, motile, Gram-negative, non-spore-forming rod that is an effective nitrogen fixing microsymbiont on the perennial clovers originating from Europe and the Mediterranean basin. TA1 however is ineffective with many annual and perennial clovers originating from Africa and America. Here we describe the features of R. leguminosarum bv. trifolii strain TA1, together with genome sequence information and annotation. The 8,618,824 bp high-quality-draft genome is arranged in a 6 scaffold of 32 contigs, contains 8,493 protein-coding genes and 83 RNA-only encoding genes, and is one of 20 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Community Sequencing Program. 相似文献
44.
Jason Terpolilli Yvette Hill Rui Tian John Howieson Lambert Br?u Lynne Goodwin James Han Konstantinos Liolios Marcel Huntemann Amrita Pati Tanja Woyke Konstantinos Mavromatis Victor Markowitz Natalia Ivanova Nikos Kyrpides Wayne Reeve 《Standards in genomic sciences》2013,9(2):315-324
Ensifer meliloti WSM1022 is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of Medicago. WSM1022 was isolated in 1987 from a nodule recovered from the roots of the annual Medicago orbicularis growing on the Cyclades Island of Naxos in Greece. WSM1022 is highly effective at fixing nitrogen with M. truncatula and other annual species such as M. tornata and M. littoralis and is also highly effective with the perennial M. sativa (alfalfa or lucerne). In common with other characterized E. meliloti strains, WSM1022 will nodulate but fixes poorly with M. polymorpha and M. sphaerocarpos and does not nodulate M. murex. Here we describe the features of E. meliloti WSM1022, together with genome sequence information and its annotation. The 6,649,661 bp high-quality-draft genome is arranged into 121 scaffolds of 125 contigs containing 6,323 protein-coding genes and 75 RNA-only encoding genes, and is one of 100 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project. 相似文献
45.
46.
Rai Dilip Toshiyuki Ishii Hideki Imada Yuko Wada-Kiyama Ryoiti Kiyama Eiichi Miyachi Makoto Kaneda 《Journal of molecular histology》2013,44(6):639-644
There is increasing evidence that ATP acts on purinergic receptors and mediates synaptic transmission in the retina. In a previous study, we raised the possibility that P2X-purinoceptors, presumably P2X2-purinoceptors in OFF-cholinergic amacrine cells, play a key role in the formation of OFF pathway-specific modulation. In this study, we examined whether the P2Y1-purinoceptors can function in cholinergic amacrine cells in the mouse retina since cholinergic amacrine cells in the rat retina express P2Y1-purinoceptors. P2Y1-purinoceptors were shown to be expressed in dendrites of both ON- and OFF-cholinergic amacrine cells in adults. At postnatal day 7, there was immunoreactivity for P2Y1-purinoceptors in the soma of cholinergic amacrine cells. At postnatal day 14, weak immunoreactivity for P2Y1-purinoceptors was detected in the dendrites but not in the soma of cholinergic amacrine cells. At postnatal day 21, strong immunoreactivity for P2Y1-purinoceptors was detected in dendrites of cholinergic amacrine cells. The expression pattern of P2Y1-purinoceptors was not affected by visual experience. We concluded that P2Y1-purinoceptors are not involved in the OFF-pathway-specific signal transmission in cholinergic amacrine cells of the mouse retina. 相似文献
47.
Chandana Basu Mallick Florin Mircea Iliescu M?rt M?ls Sarah Hill Rakesh Tamang Gyaneshwer Chaubey Rie Goto Simon Y. W. Ho Irene Gallego Romero Federica Crivellaro Georgi Hudjashov Niraj Rai Mait Metspalu C. G. Nicholas Mascie-Taylor Ramasamy Pitchappan Lalji Singh Marta Mirazon-Lahr Kumarasamy Thangaraj Richard Villems Toomas Kivisild 《PLoS genetics》2013,9(11)
Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India. 相似文献
48.
Amrita L. Sherlekar Abbey Janssen Meagan S. Siehr Pamela K. Koo Laura Caflisch May Boggess Robyn Lints 《PloS one》2013,8(4)
Background
Mating behaviors in simple invertebrate model organisms represent tractable paradigms for understanding the neural bases of sex-specific behaviors, decision-making and sensorimotor integration. However, there are few examples where such neural circuits have been defined at high resolution or interrogated.Methodology/Principal Findings
Here we exploit the simplicity of the nematode Caenorhabditis elegans to define the neural circuits underlying the male’s decision to initiate mating in response to contact with a mate. Mate contact is sensed by male-specific sensilla of the tail, the rays, which subsequently induce and guide a contact-based search of the hermaphrodite’s surface for the vulva (the vulva search). Atypically, search locomotion has a backward directional bias so its implementation requires overcoming an intrinsic bias for forward movement, set by activity of the sex-shared locomotory system. Using optogenetics, cell-specific ablation- and mutant behavioral analyses, we show that the male makes this shift by manipulating the activity of command cells within this sex-shared locomotory system. The rays control the command interneurons through the male-specific, decision-making interneuron PVY and its auxiliary cell PVX. Unlike many sex-shared pathways, PVY/PVX regulate the command cells via cholinergic, rather than glutamatergic transmission, a feature that likely contributes to response specificity and coordinates directional movement with other cholinergic-dependent motor behaviors of the mating sequence. PVY/PVX preferentially activate the backward, and not forward, command cells because of a bias in synaptic inputs and the distribution of key cholinergic receptors (encoded by the genes acr-18, acr-16 and unc-29) in favor of the backward command cells.Conclusion/Significance
Our interrogation of male neural circuits reveals that a sex-specific response to the opposite sex is conferred by a male-specific pathway that renders subordinate, sex-shared motor programs responsive to mate cues. Circuit modifications of these types may make prominent contributions to natural variations in behavior that ultimately bring about speciation. 相似文献49.
Sandeep Rai Bidhubhusan Mahapatra Subhashish Sircar Pinnamaneni Yujwal Raj Srinivasan Venkatesh Mohammed Shaukat Bharat Bhusan Rewari 《PloS one》2013,8(6)
Introduction
Research in India has extensively examined the factors associated with non-adherence to antiretroviral therapy (ART) with limited focus on examining the relationship between adherence to ART regimen and survival status of HIV infected patients. This study examines the effect of optimal adherence to ART on survival status of HIV infected patients attending ART centers in Jharkhand, India.Materials and Methods
Data from a cohort of 239 HIV infected individuals who were initiated ART in 2007 were compiled from medical records retrospectively for 36 months. Socio-demographic characteristics, CD4 T cell count, presence of opportunistic infections at the time of ART initiation and ART regimen intake and survival status was collected periodically. Optimal adherence was assessed using pill count methods; patients who took <95% of the specified regimens were identified as non-adherent. Cox-proportional hazard model was used to determine the relative hazards of mortality.Results
More than three-fourths of the patients were male, on an average 34 year old and median CD4 T cell count was 118 cells/cmm at the time of ART registration. About 57% of the patients registered for ART were found to be adherent to ART. A total of 104 patients died in 358.5 patient-years of observation resulting in a mortality rate of 29 per 100 patient-years (95% confidence interval (CI): 23.9–35.2) and median survival time of 6.5 months (CI: 2.7–10.9). The mortality rate was higher among patients who were non-adherent to ART (64.5, CI: 50.5–82.4) than who were adherent (15.4, CI: 11.3–21.0). The risk of mortality was fourfold higher among individuals who were non-adherent to ART than who were adherent (Adjusted hazard ratio: 3.9, CI: 2.6–6.0).Conclusion
Adherence to ART is associated with a higher chance of survival of HIV infected patients, ascertaining the need for interventions to improve the ART adherence and early initiation of ART. 相似文献50.
Ved Prakash Kanchan Vishwakarma Vijay Pratap Singh Padmaja Rai Naleeni Ramawat Durgesh Kumar Tripathi Shivesh Sharma 《Physiologia plantarum》2020,168(2):473-489
Over the past decades the role of nitric oxide (NO) and reactive oxygen species (ROS) in signaling and cellular responses to stress has witnessed an exponential trend line. Despite advances in the subject, our knowledge of the role of NO and ROS as regulators of stress and plant growth and their implication in signaling pathways is still partial. The crosstalk between NO and ROS during root formation offers new domains to be explored, as it regulates several plant functions. Previous findings indicate that plants utilize these signaling molecules for regulating physiological responses and development. Depending upon cellular concentration, NO either can stimulate or impede root system architecture (RSA) by modulating enzymes through post-translational modifications. Similarly, the ROS signaling molecule network, in association with other hormonal signaling pathways, control the RSA. The spatial regulation of ROS controls cell growth and ROS determine primary root and act in concert with NO to promote lateral root primordia. NO and ROS are two central messenger molecules which act differentially to upregulate or downregulate the expression of genes pertaining to auxin synthesis and to the configuration of root architecture. The investigation concerning the contribution of donors and inhibitors of NO and ROS can further aid in deciphering their role in root development. With this background, this review provides comprehensive details about the effect and function of NO and ROS in the development of RSA. 相似文献