全文获取类型
收费全文 | 18266篇 |
免费 | 1630篇 |
国内免费 | 10篇 |
出版年
2022年 | 122篇 |
2021年 | 205篇 |
2020年 | 144篇 |
2019年 | 192篇 |
2018年 | 236篇 |
2017年 | 234篇 |
2016年 | 333篇 |
2015年 | 691篇 |
2014年 | 759篇 |
2013年 | 952篇 |
2012年 | 1164篇 |
2011年 | 1213篇 |
2010年 | 798篇 |
2009年 | 751篇 |
2008年 | 1024篇 |
2007年 | 1110篇 |
2006年 | 1039篇 |
2005年 | 1044篇 |
2004年 | 1029篇 |
2003年 | 851篇 |
2002年 | 852篇 |
2001年 | 264篇 |
2000年 | 217篇 |
1999年 | 245篇 |
1998年 | 276篇 |
1997年 | 161篇 |
1996年 | 135篇 |
1995年 | 125篇 |
1994年 | 141篇 |
1993年 | 128篇 |
1992年 | 157篇 |
1991年 | 142篇 |
1990年 | 123篇 |
1989年 | 151篇 |
1988年 | 112篇 |
1987年 | 136篇 |
1986年 | 109篇 |
1985年 | 136篇 |
1984年 | 124篇 |
1983年 | 120篇 |
1982年 | 136篇 |
1981年 | 121篇 |
1980年 | 97篇 |
1979年 | 93篇 |
1978年 | 83篇 |
1977年 | 95篇 |
1976年 | 73篇 |
1974年 | 93篇 |
1973年 | 79篇 |
1972年 | 67篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
831.
Dimitra Sakoula Garrett J. Smith Jeroen Frank Rob J. Mesman Linnea F. M. Kop Pieter Blom Mike S. M. Jetten Maartje A. H. J. van Kessel Sebastian Lücker 《The ISME journal》2022,16(4):958
The advance of metagenomics in combination with intricate cultivation approaches has facilitated the discovery of novel ammonia-, methane-, and other short-chain alkane-oxidizing microorganisms, indicating that our understanding of the microbial biodiversity within the biogeochemical nitrogen and carbon cycles still is incomplete. The in situ detection and phylogenetic identification of novel ammonia- and alkane-oxidizing bacteria remain challenging due to their naturally low abundances and difficulties in obtaining new isolates from complex samples. Here, we describe an activity-based protein profiling protocol allowing cultivation-independent unveiling of ammonia- and alkane-oxidizing bacteria. In this protocol, 1,7-octadiyne is used as a bifunctional enzyme probe that, in combination with a highly specific alkyne-azide cycloaddition reaction, enables the fluorescent or biotin labeling of cells harboring active ammonia and alkane monooxygenases. Biotinylation of these enzymes in combination with immunogold labeling revealed the subcellular localization of the tagged proteins, which corroborated expected enzyme targets in model strains. In addition, fluorescent labeling of cells harboring active ammonia or alkane monooxygenases provided a direct link of these functional lifestyles to phylogenetic identification when combined with fluorescence in situ hybridization. Furthermore, we show that this activity-based labeling protocol can be successfully coupled with fluorescence-activated cell sorting for the enrichment of nitrifiers and alkane-oxidizing bacteria from complex environmental samples, enabling the recovery of high-quality metagenome-assembled genomes. In conclusion, this study demonstrates a novel, functional tagging technique for the reliable detection, identification, and enrichment of ammonia- and alkane-oxidizing bacteria present in complex microbial communities.Subject terms: Environmental microbiology, Sequencing, Microbiology 相似文献
832.
833.
Denis Tvorogov Chloe A L ThompsonPeach Johannes Foßelteder Mara Dottore Frank Stomski Suraiya A Onnesha Kelly Lim Paul A B Moretti Stuart M Pitson David M Ross Andreas Reinisch Daniel Thomas Angel F Lopez 《EMBO reports》2022,23(4)
Calreticulin (CALR) is recurrently mutated in myelofibrosis via a frameshift that removes an endoplasmic reticulum retention signal, creating a neoepitope potentially targetable by immunotherapeutic approaches. We developed a specific rat monoclonal IgG2α antibody, 4D7, directed against the common sequence encoded by both insertion and deletion mutations. 4D7 selectively bound to cells co‐expressing mutant CALR and thrombopoietin receptor (TpoR) and blocked JAK‐STAT signalling, TPO‐independent proliferation and megakaryocyte differentiation of mutant CALR myelofibrosis progenitors by disrupting the binding of CALR dimers to TpoR. Importantly, 4D7 inhibited proliferation of patient samples with both insertion and deletion CALR mutations but not JAK2 V617F and prolonged survival in xenografted bone marrow models of mutant CALR‐dependent myeloproliferation. Together, our data demonstrate a novel therapeutic approach to target a problematic disease driven by a recurrent somatic mutation that would normally be considered undruggable. 相似文献
834.
Soumyaparna Das Valerie Popp Michael Power Kathrin Groeneveld Jie Yan Christian Melle Luke Rogerson Marlly Achury Frank Schwede Torsten Strasser Thomas Euler Franois Paquet-Durand Vasilica Nache 《Cell death & disease》2022,13(1)
Hereditary degeneration of photoreceptors has been linked to over-activation of Ca2+-permeable channels, excessive Ca2+-influx, and downstream activation of Ca2+-dependent calpain-type proteases. Unfortunately, after more than 20 years of pertinent research, unequivocal evidence proving significant and reproducible photoreceptor protection with Ca2+-channel blockers is still lacking. Here, we show that both D- and L-cis enantiomers of the anti-hypertensive drug diltiazem were very effective at blocking photoreceptor Ca2+-influx, most probably by blocking the pore of Ca2+-permeable channels. Yet, unexpectedly, this block neither reduced the activity of calpain-type proteases, nor did it result in photoreceptor protection. Remarkably, application of the L-cis enantiomer of diltiazem even led to a strong increase in photoreceptor cell death. These findings shed doubt on the previously proposed links between Ca2+ and retinal degeneration and are highly relevant for future therapy development as they may serve to refocus research efforts towards alternative, Ca2+-independent degenerative mechanisms.Subject terms: Cell death in the nervous system, Ion channels in the nervous system, Molecular neuroscience 相似文献
835.
Bingchuan Wei Nicholas Woon Lu Dai Raphael Fish Michelle Tai Winode Handagama Ashley Yin Jia Sun Andrew Maier Dana McDaniel Elvira Kadaub Jessica Yang Miguel Saggu Ann Woys Oxana Pester Danny Lambert Alex Pell Zhiqi Hao Gordon Magill Jack Yim Jefferson Chan Lindsay Yang Frank Macchi Christian Bell Galahad Deperalta Yan Chen 《MABS-AUSTIN》2022,14(1)
836.
In response to stressful growth conditions of high population density, food scarcity, and elevated temperature, young larvae of nematode Caenorhabditis elegans can enter a developmentally arrested stage called dauer that is characterized by dramatic anatomic and metabolic remodeling. Genetic analysis of dauer formation of C. elegans has served as an experimental paradigm for the identification and characterization of conserved neuroendocrine signaling pathways. Here, we report the identification and characterization of a conserved c-Jun N-terminal Kinase-like mitogen-activated protein kinase (MAPK) pathway that is required for dauer formation in response to environmental stressors. We observed that loss-of-function mutations in the MLK-1-MEK-1-KGB-1 MAPK pathway suppress dauer entry. A loss-of-function mutation in the VHP-1 MAPK phosphatase, a negative regulator of KGB-1 signaling, results in constitutive dauer formation, which is dependent on the presence of dauer pheromone but independent of diminished food levels or elevated temperatures. Our data suggest that the KGB-1 pathway acts in the sensory neurons, in parallel to established insulin and TGF- signaling pathways, to transduce the dauer-inducing environmental cues of diminished food levels and elevated temperature. 相似文献
837.
Martijn J. A. Weterings Sanne Losekoot Henry J. Kuipers Herbert H. T. Prins Frank van Langevelde Sipke E. van Wieren 《Ecology and evolution》2022,12(1)
- We assessed the hypothesized negative correlation between the influence of multiple predators and body condition and fecundity of the European hare, from 13 areas in the Netherlands.
- Year‐round abundance of predators was estimated by hunters. We quantified predator influence as the sum of their field metabolic rates, as this sum reflects the daily food requirements of multiple individuals. We determined the ratio between body mass and hindfoot length of hares as an index of body condition and the weight of their adrenal gland as a measure of chronic exposure to stress, and we counted the number of placental scars to estimate fecundity of hares.
- As hypothesized, we found that the sum of field metabolic rate of predators was negatively correlated with body condition and the number of placental scars, whereas it was positively related to the weight of the adrenal glands. In contrast to the sum of the field metabolic rate, the total number of predators did not or weakly affect the investigated risk responses.
- The sum of the field metabolic rate can be a useful proxy for the influence of multiple predators and takes into account predator abundance, type, body weight, and food requirements of multiple predators.
- With our findings, our paper contributes to a better understanding of the risk effects of multiple predators on prey fitness. Additionally, we identify a potential contributor to the decline of European hare populations.
838.
839.
The potential role(s) of DNA topoiosmerase II (topo II) during chromatin changes that characterize different stages of spermatogenesis was investigated in the rat by an analysis of the expression and localization of topo II mRNA and protein in individual spermatogenic cells. Expression of topo II was restricted to spermatogonia, spermatocytes, and round and early-elongating spermatids. Two protein bands of 177 and 170 kDa were detected in immunoblots of spermatocytes and round spermatids, while bands of 148 and 142 kDa were prominent in preparations of elongating spermatids. Topo II levels and distribution patterns, as observed by immunofluorescent microscopy, exhibited cell type-specific variations. Differences in topo II staining patterns were also apparent when nuclear matrices of spermatogenic cells were prepared with different extraction conditions. In addition to its possible function as a structural component, topo II, associated with nuclear matrix preparations from spermatogenic cells, possessed catalytic activity. These observations indicate that both the 177 and 170 kDa and the 148 and 142 kDa forms of topo II share similar structural and functional properties. Topo IIβ mRNA was transcribed in rat spermatogenic cells at 6.2 kb. Relative levels of topo IIβ mRNA were high in spermatogonia and spermatocytes, and decreased in both round and early-elongating spermatids. Changes in topo II expression levels and localization patterns represent distinct stage-specific markers for the maturation of spermatogenic cells, and are consistent with the involvement of topo II in mediating DNA modifications and chromatin changes during spermatogenesis. © 1996 Wiley-Liss, Inc. 相似文献
840.
A coaxial cable can be used to reduce the magnetic and electric fields that extend into environments in the vicinity of transmission lines and distribution lines and in-house or building wiring for power distribution systems. The use of the coaxial geometry may prove useful in cases where there are environmental concerns with respect to health effects and in cases where there is a need to run high-speed data communications in close proximity to power distribution systems. © 1996 Wiley-Liss, Inc. 相似文献