全文获取类型
收费全文 | 37449篇 |
免费 | 118篇 |
国内免费 | 211篇 |
专业分类
系统科学 | 206篇 |
丛书文集 | 517篇 |
教育与普及 | 61篇 |
理论与方法论 | 137篇 |
现状及发展 | 17907篇 |
研究方法 | 1535篇 |
综合类 | 16907篇 |
自然研究 | 508篇 |
出版年
2013年 | 303篇 |
2012年 | 542篇 |
2011年 | 1026篇 |
2010年 | 234篇 |
2008年 | 686篇 |
2007年 | 744篇 |
2006年 | 777篇 |
2005年 | 697篇 |
2004年 | 696篇 |
2003年 | 662篇 |
2002年 | 694篇 |
2001年 | 1148篇 |
2000年 | 1096篇 |
1999年 | 761篇 |
1992年 | 731篇 |
1991年 | 533篇 |
1990年 | 611篇 |
1989年 | 607篇 |
1988年 | 590篇 |
1987年 | 666篇 |
1986年 | 599篇 |
1985年 | 763篇 |
1984年 | 647篇 |
1983年 | 490篇 |
1982年 | 468篇 |
1981年 | 494篇 |
1980年 | 587篇 |
1979年 | 1195篇 |
1978年 | 1035篇 |
1977年 | 932篇 |
1976年 | 832篇 |
1975年 | 829篇 |
1974年 | 1042篇 |
1973年 | 940篇 |
1972年 | 967篇 |
1971年 | 1080篇 |
1970年 | 1380篇 |
1969年 | 1014篇 |
1968年 | 1079篇 |
1967年 | 1036篇 |
1966年 | 892篇 |
1965年 | 636篇 |
1964年 | 237篇 |
1959年 | 325篇 |
1958年 | 570篇 |
1957年 | 373篇 |
1956年 | 341篇 |
1955年 | 314篇 |
1954年 | 309篇 |
1948年 | 215篇 |
排序方式: 共有10000条查询结果,搜索用时 828 毫秒
621.
Sophie M. Hapak Carla V. Rothlin Sourav Ghosh 《Cellular and molecular life sciences : CMLS》2018,75(15):2735-2761
Polarity is a fundamental feature of cells. Protein complexes, including the PAR3–PAR6–aPKC complex, have conserved roles in establishing polarity across a number of eukaryotic cell types. In neurons, polarity is evident as distinct axonal versus dendritic domains. The PAR3, PAR6, and aPKC proteins also play important roles in neuronal polarization. During this process, either aPKC kinase activity, the assembly of the PAR3–PAR6–aPKC complex or the localization of these proteins is regulated downstream of a number of signaling pathways. In turn, the PAR3, PAR6, and aPKC proteins control various effector molecules to establish neuronal polarity. Herein, we discuss the many signaling mechanisms and effector functions that have been linked to PAR3, PAR6, and aPKC during the establishment of neuronal polarity. 相似文献
622.
Qingdi Quentin Li Iawen Hsu Thomas Sanford Reema Railkar Navin Balaji Carole Sourbier Cathy Vocke K. C. Balaji Piyush K. Agarwal 《Cellular and molecular life sciences : CMLS》2018,75(5):939-963
The protein kinase D (PKD) family of proteins are important regulators of tumor growth, development, and progression. CRT0066101, an inhibitor of PKD, has antitumor activity in multiple types of carcinomas. However, the effect and mechanism of CRT0066101 in bladder cancer are not understood. In the present study, we show that CRT0066101 suppressed the proliferation and migration of four bladder cancer cell lines in vitro. We also demonstrate that CRT0066101 blocked tumor growth in a mouse flank xenograft model of bladder cancer. To further assess the role of PKD in bladder carcinoma, we examined the three PKD isoforms and found that PKD2 was highly expressed in eight bladder cancer cell lines and in urothelial carcinoma tissues from the TCGA database, and that short hairpin RNA (shRNA)-mediated knockdown of PKD2 dramatically reduced bladder cancer growth and invasion in vitro and in vivo, suggesting that the effect of the compound in bladder cancer is mediated through inhibition of PKD2. This notion was corroborated by demonstrating that the levels of phospho-PKD2 were markedly decreased in CRT0066101-treated bladder tumor explants. Furthermore, our cell cycle analysis by flow cytometry revealed that CRT0066101 treatment or PKD2 silencing arrested bladder cancer cells at the G2/M phase, the arrest being accompanied by decreases in the levels of cyclin B1, CDK1 and phospho-CDK1 (Thr161) and increases in the levels of p27Kip1 and phospho-CDK1 (Thr14/Tyr15). Moreover, CRT0066101 downregulated the expression of Cdc25C, which dephosphorylates/activates CDK1, but enhanced the activity of the checkpoint kinase Chk1, which inhibits CDK1 by phosphorylating/inactivating Cdc25C. Finally, CRT0066101 was found to elevate the levels of Myt1, Wee1, phospho-Cdc25C (Ser216), Gadd45α, and 14-3-3 proteins, all of which reduce the CDK1-cyclin B1 complex activity. These novel findings suggest that CRT0066101 suppresses bladder cancer growth by inhibiting PKD2 through induction of G2/M cell cycle arrest, leading to the blockade of cell cycle progression. 相似文献
623.
Dominik C. Fuhrmann Ilka Wittig Stefan Dröse Tobias Schmid Nathalie Dehne Bernhard Brüne 《Cellular and molecular life sciences : CMLS》2018,75(16):3051-3067
Cell stress such as hypoxia elicits adaptive responses, also on the level of mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF) 1α. Adaptation of mitochondria towards acute hypoxic conditions is reasonably well understood, while regulatory mechanisms, especially of respiratory chain assembly factors, under chronic hypoxia remains elusive. One of these assembly factors is transmembrane protein 126B (TMEM126B). This protein is part of the mitochondrial complex I assembly machinery. We identified changes in complex I abundance under chronic hypoxia, in association with impaired substrate-specific mitochondrial respiration. Complexome profiling of isolated mitochondria of the human leukemia monocytic cell line THP-1 revealed HIF-1α-dependent deficits in complex I assembly and mitochondrial complex I assembly complex (MCIA) abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1-dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1α induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (β-TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B. Attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B. 相似文献
624.
Jana Fischer Gunnar Kleinau Claudia Rutz Denise Zwanziger Noushafarin Khajavi Anne Müller Maren Rehders Klaudia Brix Catherine L. Worth Dagmar Führer Heiko Krude Burkhard Wiesner Ralf Schülein Heike Biebermann 《Cellular and molecular life sciences : CMLS》2018,75(12):2227-2239
G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and release. Indeed, we demonstrate strong interaction between both the proteins which causes a suppressed activation of Gq/11 by TSH-stimulated TSHR. Thus, we provide not only evidence for a novel interaction between the TSHR and MCT8, but could also prove this interaction on a single molecule level. Moreover, this interaction forces biased signaling at the TSHR. These results are of general interest for both the GPCR and the MFS research fields. 相似文献
625.
626.
627.
J. D. Trout has recently developed a new defense of scientific realism, a new version of the No Miracles Argument. I critically evaluate Trout's novel defense of realism. I argue that Trout's argument for scientific realism and the related explanation for the success of science are self-defeating. In the process of arguing against the traditional realist strategies for explaining the success of science, he inadvertently undermines his own argument. 相似文献
628.
629.
Jesse M. Meik Sarah Schaack Oscar Flores-Villela Jeffrey W. Streicher 《Journal of Natural History》2018,52(13-16):989-1016
ABSTRACTWe describe two diminutive species of rattlesnakes (genus Crotalus) from small nearshore islands off the coast of Baja California in the western Gulf of California, Mexico. In order to test the hypothesis that some island populations represent cohesive species entities, we applied linear discriminant analysis and uniform validation procedures to multiple classes of intrinsic trait data. By using previously recognised species to establish a threshold for species recognition, we found that assignment of specimens to either new species was as probable as with other established rattlesnake species within the speckled rattlesnake (Crotalus mitchellii) complex. We also found that assignment of specimens from other island populations was not as probable as for the established species, and these populations are referable to C. pyrrhus. The species endemic to Piojo Island is most closely related to other island and mainland populations of C. pyrrhus whereas the species endemic to Cabeza de Caballo Island is apparently most closely related to C. angelensis, a nearby island endemic of large body size. However, patterns from both mitochondrial and nuclear phylogenies, and phenotypic variation, indicate that evolutionary trajectories of both of these species have been influenced by introgression from C. angelensis. We speculate that collective evidence based on contrasting patterns of nuclear and mitochondrial evolution supports a hybrid origin of the species from Cabeza de Caballo Island followed by exceptionally rapid mitochondrial evolution. Consistent with small body size, both species show a reduction in various scale counts relative to other species of the C. mitchellii species complex, suggesting that dwarfism is not simply a plastic response to insular conditions.http://www.zoobank.org/urn.lsid:zoobank.org:pub:FBC8A11B-04A3-4231-85CA-3972DF5A42FF 相似文献
630.