全文获取类型
收费全文 | 3861篇 |
免费 | 304篇 |
国内免费 | 1篇 |
出版年
2021年 | 36篇 |
2020年 | 19篇 |
2019年 | 27篇 |
2018年 | 35篇 |
2017年 | 44篇 |
2016年 | 66篇 |
2015年 | 81篇 |
2014年 | 120篇 |
2013年 | 174篇 |
2012年 | 169篇 |
2011年 | 208篇 |
2010年 | 122篇 |
2009年 | 106篇 |
2008年 | 169篇 |
2007年 | 181篇 |
2006年 | 184篇 |
2005年 | 151篇 |
2004年 | 208篇 |
2003年 | 163篇 |
2002年 | 154篇 |
2001年 | 154篇 |
2000年 | 167篇 |
1999年 | 123篇 |
1998年 | 46篇 |
1997年 | 48篇 |
1996年 | 32篇 |
1995年 | 48篇 |
1994年 | 38篇 |
1993年 | 30篇 |
1992年 | 92篇 |
1991年 | 83篇 |
1990年 | 72篇 |
1989年 | 86篇 |
1988年 | 75篇 |
1987年 | 86篇 |
1986年 | 59篇 |
1985年 | 73篇 |
1984年 | 50篇 |
1983年 | 30篇 |
1982年 | 31篇 |
1981年 | 26篇 |
1979年 | 37篇 |
1978年 | 20篇 |
1977年 | 20篇 |
1975年 | 15篇 |
1974年 | 22篇 |
1973年 | 28篇 |
1972年 | 15篇 |
1971年 | 16篇 |
1966年 | 17篇 |
排序方式: 共有4166条查询结果,搜索用时 31 毫秒
991.
Many higher plants contain novel metabolites with antimicrobial, antifungal and antiviral properties. However, in the developed world almost all clinically used chemotherapeutics have been produced by in vitro chemical synthesis. Exceptions, like taxol and vincristine, were structurally complex metabolites that were difficult to synthesize in vitro. Many non-natural, synthetic drugs cause severe side effects that were not acceptable except as treatments of last resort for terminal diseases such as cancer. The metabolites discovered in medicinal plants may avoid the side effect of synthetic drugs, because they must accumulate within living cells. The aim here was to test an aqueous extract from the young developing leaves of willow (Salix safsaf, Salicaceae) trees for activity against human carcinoma cells in vivo and in vitro. In vivo Ehrlich Ascites Carcinoma Cells (EACC) were injected into the intraperitoneal cavity of mice. The willow extract was fed via stomach tube. The (EACC) derived tumor growth was reduced by the willow extract and death was delayed (for 35 days). In vitro the willow extract could kill the majority (75%-80%) of abnormal cells among primary cells harvested from seven patients with acute lymphoblastic leukemia (ALL) and 13 with AML (acute myeloid leukemia). DNA fragmentation patterns within treated cells inferred targeted cell death by apoptosis had occurred. The metabolites within the willow extract may act as tumor inhibitors that promote apoptosis, cause DNA damage, and affect cell membranes and/or denature proteins. 相似文献
992.
993.
The tripartite tubular mastigoneme on the anterior flagellum is a morphological feature that characterizes the stramenopiles. Mastigonemes are significant and potentially informative structures not only from the viewpoint of systematics, but also of cell biology. Nevertheless, few biochemical studies have been reported on stramenopile mastigonemes. The flagella of Scytosiphon lomentaria (Phaeophyceae) were successfully isolated and analyzed using SDS-PAGE followed by protein sequencing. The partial amino acid sequence of one flagellar protein (115kDa) showed high similarity with the sexually induced gene 1 (sig1) product of centric diatoms. A polyclonal antibody against the 115-kDa protein reacted not only to the shaft of mastigonemes in Scytosiphon lomentaria, but also another distinctly different stramenopile flagellate, Sulcochrysis biplastida (Dictyochophyceae). Therefore, we propose that the 115-kDa protein (i.e. Sig1 homologs) is a constituent of the tubular shaft of the mastigoneme. 相似文献
994.
Sau Pinn Woo Zulfigar Yasin Shau Hwai Tan Hiroshi Kajihara Toshihiko Fujita 《ZooKeys》2015,(545):1-26
Five sea cucumber species including one new species of the genus Stichopus are reported from the shallow coral reefs of Straits of Malacca. The new species Stichopus
fusiformiossa has unusual fusiform spicules in the tentacles, which are not found in the other species of the genus. Pseudo-tables and large perforated plates are newly recorded for Stichopus
hermanni Semper, 1868 and Stichopus
vastus Sluiter, 1887, respectively. 相似文献
995.
996.
Sekine Y Yamamoto C Kakisaka M Muromoto R Kon S Ashitomi D Fujita N Yoshimura A Oritani K Matsuda T 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(12):6194-6204
We found that an adaptor protein, signal-transducing adaptor protein (STAP)-2, is a new member of the Fas-death-inducing signaling complex and participates in activation-induced cell death in T cells. STAP-2 enhanced Fas-mediated apoptosis and caspase-8 aggregation and activation in Jurkat T cells. Importantly, STAP-2 directly interacted with caspase-8 and Fas, resulting in enhanced interactions between caspase-8 and FADD in the Fas-death-inducing signaling complex. Moreover, STAP-2 protein has a consensus caspase-8 cleavage sequence, VEAD, in its C-terminal domain, and processing of STAP-2 by caspase-8 was crucial for Fas-induced apoptosis. Physiologic roles of STAP-2 were confirmed by observations that STAP-2-deficient mice displayed impaired activation-induced cell death and superantigen-induced T cell depletion. Therefore, STAP-2 is a novel participant in the regulation of T cell apoptosis after stimulation. 相似文献
997.
Egawa N Nakahara T Ohno S Narisawa-Saito M Yugawa T Fujita M Yamato K Natori Y Kiyono T 《Journal of virology》2012,86(6):3276-3283
Papillomavirus genomes are thought to be amplified to about 100 copies per cell soon after infection, maintained constant at this level in basal cells, and amplified for viral production upon keratinocyte differentiation. To determine the requirement for E1 in viral DNA replication at different stages, an E1-defective mutant of the human papillomavirus 16 (HPV16) genome featuring a translation termination mutation in the E1 gene was used. The ability of the mutant HPV16 genome to replicate as nuclear episomes was monitored with or without exogenous expression of E1. Unlike the wild-type genome, the E1-defective HPV16 genome became established in human keratinocytes only as episomes in the presence of exogenous E1 expression. Once established, it could replicate with the same efficiency as the wild-type genome, even after the exogenous E1 was removed. However, upon calcium-induced keratinocyte differentiation, once again amplification was dependent on exogenous E1. These results demonstrate that the E1 protein is dispensable for maintenance replication but not for initial and productive replication of HPV16. 相似文献
998.
Kanzawa N Shimozawa N Wanders RJ Ikeda K Murakami Y Waterham HR Mukai S Fujita M Maeda Y Taguchi R Fujiki Y Kinoshita T 《Journal of lipid research》2012,53(4):653-663
Many cell surface proteins in mammalian cells are anchored to the plasma membrane via glycosylphosphatidylinositol (GPI). The predominant form of mammalian GPI contains 1-alkyl-2-acyl phosphatidylinositol (PI), which is generated by lipid remodeling from diacyl PI. The conversion of diacyl PI to 1-alkyl-2-acyl PI occurs in the ER at the third intermediate in the GPI biosynthetic pathway. This lipid remodeling requires the alkyl-phospholipid biosynthetic pathway in peroxisome. Indeed, cells defective in dihydroxyacetone phosphate acyltransferase (DHAP-AT) or alkyl-DHAP synthase express only the diacyl form of GPI-anchored proteins. A defect in the alkyl-phospholipid biosynthetic pathway causes a peroxisomal disorder, rhizomelic chondrodysplasia punctata (RCDP), and defective biogenesis of peroxisomes causes Zellweger syndrome, both of which are lethal genetic diseases with multiple clinical phenotypes such as psychomotor defects, mental retardation, and skeletal abnormalities. Here, we report that GPI lipid remodeling is defective in cells from patients with Zellweger syndrome having mutations in the peroxisomal biogenesis factors PEX5, PEX16, and PEX19 and in cells from patients with RCDP types 1, 2, and 3 caused by mutations in PEX7, DHAP-AT, and alkyl-DHAP synthase, respectively. Absence of the 1-alkyl-2-acyl form of GPI-anchored proteins might account for some of the complex phenotypes of these two major peroxisomal disorders. 相似文献
999.
Takahashi K Makita N Manaka K Hisano M Akioka Y Miura K Takubo N Iida A Ueda N Hashimoto M Fujita T Igarashi T Sekine T Iiri T 《The Journal of biological chemistry》2012,287(3):2099-2106
Inactivating mutations of the V2 vasopressin receptor (V2R) cause cross-linked congenital nephrogenic diabetes insipidus (NDI), resulting in renal resistance to the antidiuretic hormone AVP. In two families showing partial NDI, characterized by an apparently normal response to diagnostic tests and an increase in the basal ADH levels suggesting AVP resistance, we have identified two V2R mutations, Ser-333del and Y128S. Both mutant V2Rs, when expressed in COS-7 cells, show partial defects in vasopressin-stimulated cAMP accumulation and intracellular localization. The inhibition of internalization does not rescue their localization. In contrast, the non-peptide V2R antagonists OPC41061 and OPC31260 partially rescue the membrane localization and basal function of these V2R mutants, whereas they inhibit the basal activity of the wild-type V2R. These results indicate that a partial loss of function of Ser-333del and Y128S mutant V2Rs results from defective membrane trafficking. These findings further indicate that V2R antagonists can act as protean agonists, serving as pharmacological chaperones for inactivating V2R mutants and also as inverse agonists of wild-type receptors. We speculate that this protean agonism could underlie the possible dual beneficial effects of the V2R antagonist: improvement of hyponatremia with heart failure or polycystic kidney disease and potential rescue of NDI. 相似文献
1000.