全文获取类型
收费全文 | 20264篇 |
免费 | 1967篇 |
国内免费 | 634篇 |
出版年
2023年 | 118篇 |
2022年 | 236篇 |
2021年 | 482篇 |
2020年 | 331篇 |
2019年 | 425篇 |
2018年 | 495篇 |
2017年 | 370篇 |
2016年 | 616篇 |
2015年 | 999篇 |
2014年 | 1097篇 |
2013年 | 1291篇 |
2012年 | 1505篇 |
2011年 | 1481篇 |
2010年 | 973篇 |
2009年 | 766篇 |
2008年 | 1052篇 |
2007年 | 984篇 |
2006年 | 937篇 |
2005年 | 855篇 |
2004年 | 787篇 |
2003年 | 755篇 |
2002年 | 681篇 |
2001年 | 563篇 |
2000年 | 498篇 |
1999年 | 460篇 |
1998年 | 228篇 |
1997年 | 207篇 |
1996年 | 188篇 |
1995年 | 174篇 |
1994年 | 154篇 |
1993年 | 126篇 |
1992年 | 250篇 |
1991年 | 247篇 |
1990年 | 209篇 |
1989年 | 219篇 |
1988年 | 195篇 |
1987年 | 155篇 |
1986年 | 147篇 |
1985年 | 175篇 |
1984年 | 125篇 |
1983年 | 99篇 |
1982年 | 93篇 |
1981年 | 99篇 |
1979年 | 111篇 |
1978年 | 94篇 |
1977年 | 73篇 |
1976年 | 70篇 |
1975年 | 95篇 |
1974年 | 93篇 |
1973年 | 88篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Seung Hyun Han Seongjun Kim Hanna Chang Hyun-Jun Kim Asia Khamzina Yowhan Son 《Journal of Plant Ecology》2019,12(5):871
Aims
Assessment of factors regulating root decomposition is needed to understand carbon and nutrient cycling in forest ecosystems. The objective of this study is to examine the effects of soil depth and root diameter on root decomposition and to analyze the relationship of root decomposition with factors such as soil environmental conditions and initial litter quality. 相似文献
992.
Meeja Seo Jeong Hwan Kim Bo Yoon Seo Changgyu Park Byeong Ryeol Choi Kwang Ho Kim Chang Woo Ji Jum Rae Cho 《Journal of Asia》2019,22(4):1013-1018
Anastatus orientalis is a solitary endoparasitoid of Lycorma delicatula (Hemiptera: Fulgoridae) eggs. We investigated the development, longevity, fecundity, and sex ratio of A. orientalis on different temperatures to establish the optimal temperature condition for laboratory mass rearing. There were significant differences in its development and longevity between 15 °C and the rest of temperature conditions (20, 25, and 30 °C), among which were no significant differences. The average number of eggs laid by A. orientalis was higher at 20 and 25 °C, but there was no statistically significant difference in its fecundity between the two temperatures. More females emerged at 15 and 20 °C than higher temperatures.Parasitisms of A. orientalis varied with host egg ages and densities. Even in 14 day old eggs of L. delicatula, parasitoids successfully emerged from 92.3% of the parasitized eggs. On the other hand, parasitism was lowest (13.8%) on just before hatching eggs. Parasitism was negatively dependent on host density.Oviposition behavior for A. orientalis primarily occurred at 1400–1600 h, not at 2400–0800 h. The majority of this parasitoid's emergence occurred at 0800–1000 h, largely before noon. These results may be useful for controlling the adequate time for supplying host eggs and release density of this parasitoid as well as for potentially predicting the accurate time for securing parasitoid adults in laboratory mass rearing of A. orientalis. 相似文献
993.
994.
Jin Zhou Xiao‐Hui Dong Feng‐Zhi Zhang Hui‐Min Zhu Tong Hao Xiao‐Xia Jiang Wei‐Bo Zheng Tao Zhang Pei‐Zhe Wang Hong Li Jie Na Chang‐Yong Wang 《Cell proliferation》2019,52(3)
Induced pluripotent stem cells (iPSCs) are reprogrammed somatic cells that gained self‐renewal and differentiation capacity similar to embryonic stem cells. Taking the precious opportunity of the TianZhou‐1 spacecraft mission, we studied the effect of space microgravity (µg) on the self‐renewal capacity of iPSCs. Murine iPSCs carrying pluripotency reporter Oct4‐GFP were used. The Oct4‐EGFP‐iPSCs clones were loaded into the bioreactor and exposed to μg in outer space for 14 days. The control experiment was performed in identical device but on the ground in earth gravity (1 g). iPSCs clones were compact and highly expressed Oct4 before launch. In μg condition, cells in iPSC clones spread out more rapidly than those in ground 1 g condition during the first 3 days after launch. However, in 1 g condition, as the cell density increases, the Oct4‐GFP signal dropped significantly during the following 3 days. Interestingly, in μg condition, iPSCs originated from the spread‐out clones during the first 3 days appeared to cluster together and reform colonies that activated strong Oct4 expression. On the other hand, iPSC clones in 1 g condition were not able to recover Oct4 expression after overgrown. Our study for the first time performed real‐time imaging on the proliferation process of iPSCs in space and found that in μg condition, cell behaviour appeared to be more dynamic than on the ground. 相似文献
995.
Birong Zhang James R. Kiefer Robert A. Blake Jae H. Chang Steven Hartman Ellen Rei Ingalla Tracy Kleinheinz Vidhi Mody Michelle Nannini Daniel F. Ortwine Yingqing Ran Amy Sambrone Deepak Sampath Maia Vinogradova Yu Zhong Jerome C. Nwachukwu Kendall W. Nettles Tommy Lai Jun Liang 《Bioorganic & medicinal chemistry letters》2019,29(7):905-911
Despite tremendous progress made in the understanding of the ERα signaling pathway and the approval of many therapeutic agents, ER+?breast cancer continues to be a leading cause of cancer death in women. We set out to discover compounds with a dual mechanism of action in which they not only compete with estradiol for binding with ERα, but also can induce the degradation of the ERα protein itself. We were attracted to the constrained chromenes containing a tetracyclic benzopyranobenzoxepine scaffold, which were reported as potent selective estrogen receptor modulators (SERMs). Incorporation of a fluoromethyl azetidine side chain yielded highly potent and efficacious selective estrogen receptor degraders (SERDs), such as 16aa and surprisingly, also its enantiomeric pair 16ab. Co-crystal structures of the enantiomeric pair 16aa and 16ab in complex with ERα revealed default (mimics the A-D rings of endogenous ligand estradiol) and core-flipped binding modes, rationalizing the equivalent potency observed for these enantiomers in the ERα degradation and MCF-7 anti-proliferation assays. 相似文献
996.
SAR inspired by aldehyde oxidase (AO) metabolism: Discovery of novel,CNS penetrant tricyclic M4 PAMs
Trevor C. Chopko Changho Han Alison R. Gregro Darren W. Engers Andrew S. Felts Mike S. Poslusney Katrina A. Bollinger Ryan D. Morrison Michael Bubser Atin Lamsal Vincent B. Luscombe Hyekyung P. Cho Nathalie C. Schnetz-Boutaud Alice L. Rodriguez Sichen Chang J. Scott Daniels Donald F. Stec Colleen M. Niswender Bruce J. Melancon 《Bioorganic & medicinal chemistry letters》2019,29(16):2224-2228
This letter describes progress towards an M4 PAM preclinical candidate inspired by an unexpected aldehyde oxidase (AO) metabolite of a novel, CNS penetrant thieno[2,3-c]pyridine core to an equipotent, non-CNS penetrant thieno[2,3-c]pyrdin-7(6H)-one core. Medicinal chemistry design efforts yielded two novel tricyclic cores that enhanced M4 PAM potency, regained CNS penetration, displayed favorable DMPK properties and afforded robust in vivo efficacy in reversing amphetamine-induced hyperlocomotion in rats. 相似文献
997.
Vicuna Requesens Deborah Gonzalez Romero Maria Elena Devaiah Shivakumar P. Chang Yeun-Kyung Flory Ashley Streatfield Stephen Ring Rebecca Phillips Cassie Hood Nathan C. Marbaniang Cyrus Dean Howard John A. Hood Elizabeth E. 《Transgenic research》2019,28(5-6):537-547
Transgenic Research - Expression of recombinant proteins in plants is a technology for producing vaccines, pharmaceuticals and industrial enzymes. For the past several years, we have produced... 相似文献
998.
Tai‐Wen Lin Chi‐Chih Chen Shu‐Mei Wu Yu‐Ching Chang Yi‐Chuan Li Yu‐Wang Su Chwan‐Deng Hsiao Hsin‐Yang Chang 《The Plant journal : for cell and molecular biology》2019,99(1):128-143
In mammals and yeast, tail‐anchored (TA) membrane proteins destined for the post‐translational pathway are safely delivered to the endoplasmic reticulum (ER) membrane by a well‐known targeting factor, TRC40/Get3. In contrast, the underlying mechanism for translocation of TA proteins in plants remains obscure. How this unique eukaryotic membrane‐trafficking system correctly distinguishes different subsets of TA proteins destined for various organelles, including mitochondria, chloroplasts and the ER, is a key question of long standing. Here, we present crystal structures of algal ArsA1 (the Get3 homolog) in a distinct nucleotide‐free open state and bound to adenylyl‐imidodiphosphate. This approximately 80‐kDa protein possesses a monomeric architecture, with two ATPase domains in a single polypeptide chain. It is capable of binding chloroplast (TOC34 and TOC159) and mitochondrial (TOM7) TA proteins based on features of its transmembrane domain as well as the regions immediately before and after the transmembrane domain. Several helices located above the TA‐binding groove comprise the interlocking hook‐like motif implicated by mutational analyses in TA substrate recognition. Our data provide insights into the molecular basis of the highly specific selectivity of interactions of algal ArsA1 with the correct sets of TA substrates before membrane targeting in plant cells. 相似文献
999.
Songtao Li Hongling Zhao Xiaomin Chang Jianping Wang Enhong Zhao Zhifeng Yin Xiaoxia Mao Shuhua Deng Ting Hao Huina Wang Yaqi Yang 《Journal of peptide science》2019,25(1)
Overexpression of gonadotropin‐releasing hormone (GnRH) receptor in many tumors but not in normal tissues makes it possible to use GnRH analogs as targeting peptides for selective delivery of cytotoxic agents, which may help to enhance the uptake of anticancer drugs by cancer cells and reduce toxicity to normal cells. The GnRH analogs [d ‐Cys6, desGly10, Pro9‐NH2]‐GnRH, [d ‐Cys6, desGly10, Pro9‐NHEt]‐GnRH, and [d ‐Cys6, α‐aza‐Gly10‐NH2]‐GnRH were conjugated with doxorubicin (Dox), respectively, through N‐succinimidyl‐3‐maleimidopropionate as a linker to afford three new GnRH‐Dox conjugates. The metabolic stability of these conjugates in human serum was determined by RP‐HPLC. The antiproliferative activity of the conjugates was examined in GnRH receptor‐positive MCF‐7 human breast cancer cell line by MTT assay. The three GnRH‐Dox conjugates showed improved metabolic stability in human serum in comparison with AN‐152. The antiproliferative effect of conjugate II ([d ‐Cys6, desGly10, Pro9‐NHEt]‐GnRH‐Dox) on MCF‐7 cells was higher than that of conjugate I ([d ‐Cys6, desGly10, Pro9‐NH2]‐GnRH‐Dox) and conjugate III ([d ‐Cys6, α‐aza‐Gly10‐NH2]‐GnRH‐Dox), and the cytotoxicity of conjugate II against GnRH receptor‐negative 3T3 mouse embryo fibroblast cells was decreased in comparison with free Dox. GnRH receptor inhibition test suggested that the antiproliferative activity of conjugate II might be due to the cellular uptake mediated by the targeting binding of [d ‐Cys6‐des‐Gly10‐Pro9‐NHEt]‐GnRH to GnRH receptors. Our study indicates that targeting delivery of conjugate II mediated by [d ‐Cys6‐des‐Gly10‐Pro9‐NHEt]‐GnRH is a promising strategy for chemotherapy of tumors that overexpress GnRH receptors. 相似文献
1000.
Larry M. Palato Shannon Pilcher Alissa Oakes Arleen Lamba Jaris Torres Litza I. Ledesma Monjaraz Crystabel Munoz Edward Njoo Dillon J. Rinauro Kate Alexandra Menefee Angela Tun Betssy L. Jauregui Sarah Shapiro Olivia H. Nossiff Eileen Olivares Kevin Chang Viviane Nguyen Luiza A. Nogaj David A. Moffet 《Journal of peptide science》2019,25(8)
The aggregation of the 37‐amino acid polypeptide human islet amyloid polypeptide (hIAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of human pancreatic β‐islet cells in type 2 diabetes. hIAPP is considered to be one of the most amyloidogenic proteins known. The quick aggregation of hIAPP leads to the formation of toxic species, such as oligomers and fibers, that damage mammalian cells (both human and rat pancreatic cells). Whether this toxicity is necessary for the progression of type 2 diabetes or merely a side effect of the disease remains unclear. If hIAPP aggregation into toxic amyloid is on‐path for developing type 2 diabetes in humans, islet amyloid polypeptide (IAPP) aggregation would likely need to play a similar role within other organisms known to develop the disease. In this work, we compared the aggregation potential and cellular toxicity of full‐length IAPP from several diabetic and nondiabetic organisms whose aggregation propensities had not yet been determined for full‐length IAPP. 相似文献