全文获取类型
收费全文 | 3523篇 |
免费 | 209篇 |
国内免费 | 1篇 |
专业分类
3733篇 |
出版年
2022年 | 22篇 |
2021年 | 41篇 |
2020年 | 22篇 |
2019年 | 39篇 |
2018年 | 47篇 |
2017年 | 43篇 |
2016年 | 72篇 |
2015年 | 105篇 |
2014年 | 145篇 |
2013年 | 234篇 |
2012年 | 232篇 |
2011年 | 222篇 |
2010年 | 121篇 |
2009年 | 106篇 |
2008年 | 212篇 |
2007年 | 166篇 |
2006年 | 198篇 |
2005年 | 158篇 |
2004年 | 187篇 |
2003年 | 150篇 |
2002年 | 135篇 |
2001年 | 106篇 |
2000年 | 109篇 |
1999年 | 98篇 |
1998年 | 33篇 |
1997年 | 22篇 |
1996年 | 18篇 |
1995年 | 23篇 |
1994年 | 20篇 |
1993年 | 22篇 |
1992年 | 51篇 |
1991年 | 47篇 |
1990年 | 48篇 |
1989年 | 58篇 |
1988年 | 54篇 |
1987年 | 43篇 |
1986年 | 44篇 |
1985年 | 40篇 |
1984年 | 29篇 |
1983年 | 11篇 |
1982年 | 30篇 |
1981年 | 15篇 |
1979年 | 17篇 |
1978年 | 18篇 |
1977年 | 12篇 |
1975年 | 8篇 |
1974年 | 13篇 |
1973年 | 12篇 |
1972年 | 8篇 |
1969年 | 16篇 |
排序方式: 共有3733条查询结果,搜索用时 15 毫秒
141.
142.
Nakagawa A Nagaosa K Hirose T Tsuda K Hasegawa K Shiratsuchi A Nakanishi Y 《Development, growth & differentiation》2004,46(3):283-298
Class B scavenger receptor type I (SR-BI), a multiligand membrane protein, exists in various organs and cell types. In the testis, SR-BI is expressed in two somatic cell types: Leydig cells and Sertoli cells. Unlike interstitially localized Leydig cells, Sertoli cells present within the seminiferous tubules keep contact with spermatogenic cells and form the tight junction to divide the seminiferous epithelium into the basal and adluminal compartments. In this study, the expression and function of SR-BI in rat Sertoli cells were examined with respect to dependency on the spermatogenic cycle, the plasma membrane polarity, and the pituitary hormone follicle-stimulating hormone (FSH). When the expression of SR-BI was histochemically examined with testis sections, both protein and mRNA were already present in Sertoli cells during the first-round spermatogenesis and continued to be detectable thereafter. The level of SR-BI mRNA expression in Sertoli cells was lower at spermatogenic stages I-VI than at other stages. SR-BI was present and functional (in mediating cellular incorporation of lipids of high density lipoprotein) at both the apical and basolateral surfaces of polarized Sertoli cells. Finally, SR-BI expression at both the protein and mRNA levels was stimulated by FSH in cultured Sertoli cells. These results indicate that SR-BI functions on both the apical and basolateral plasma membranes of Sertoli cells, and that SR-BI expression in Sertoli cells changes during the spermatogenic cycle and is stimulated, at least in cultures, by FSH. 相似文献
143.
144.
145.
Gotoh N Yamada R Hiratani H Renault V Kuroiwa S Monet M Toyoda S Chida S Mandai M Otani A Yoshimura N Matsuda F 《Human genetics》2006,120(1):139-143
Age-related macular degeneration (ARMD) is the leading cause of blindness in the elderly population not only Western but also Asian industrial countries. In Caucasian, a polymorphism of the complement factor H gene (CFH), the C allele of rs1061170 (Y402H), was established as the first strong genetic factor for excursively exudative type of ARMD. In this study, we performed an extensive sequencing of the 22 exons in the CFH gene by recruiting 146 exudative ARMD patients and 105 normal controls of Japanese origin and identified 61 polymorphisms. We found that the frequency of the C allele of rs1061170 (Y402H) is much lower (0.04) in Japanese controls than in Caucasians (0.45). No case disease susceptibility to exudative ARMD was noted for rs1061170 (Y402H) (χ
2 = 3.19, P
corr = 0.423), or other 12 single nucleotide polymorphisms (SNPs) whose frequency is greater than 0.05. When haplotypes were inferred for 13 SNPs (these 12 SNPs with a frequency greater than 0.05 and rs1061170), three haplotypes whose pattern was similar to those in Caucasians were identified but with substantial difference in frequency. Again we failed to identify genetic association between Japanese exudative ARMD and any of the haplotypes including the J1 haplotype which was shown to be susceptible to ARMD in Caucasians (χ
2 = 3.92, P
corr = 0.157). CFH does not appear to be a primary hereditary contributor to ARMD in Japanese. The absence of CFH contribution to ARMD in Japanese may correlate with the findings in ethnic differences of ARMD phenotypes.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.This work was accomplished by equal contribution of two groups organized by the last two authors. 相似文献
146.
Remi Nakagawa Masahiro Kurushima Masaaki Matsui Ryouichi Nakamura Takafumi Kubo Ryo Funada 《In vitro cellular & developmental biology. Plant》2011,47(4):480-487
Effects of polyamines on the development of embryonal-suspensor masses (ESMs) and the formation of somatic embryos were examined
in an effort to improve the frequency of somatic embryogenesis in Picea glehnii. Exogenous spermidine at 100 and 300 μM promoted the elongation of suspensors and the formation of somatic embryos. Exogenous
putrescine at 100 μM increased the number of somatic embryos and decreased the time required for formation of somatic embryos.
Thus, exogenous polyamines improved the maturation capacity of ESMs and promoted the formation of somatic embryos in P. glehnii. Light microscopy revealed that ESMs with high maturation capacity consisted of the three following cells: round or oval
cells, elongated cells, and protean cells. These components might be related to the capacity for formation of somatic embryos. 相似文献
147.
Cellular incorporation of Cd involves multiple transport systems for other metals such as Fe, Zn, Mn, and Ca. Metal transporters including divalent metal transporter 1, Zrt/Irt-related protein (ZIP) 8, and ZIP14, and certain types of voltage-dependent Ca channels have been shown to be involved in cellular Cd uptake. However, tissue- or cell-specific roles of these metal transporters in the accumulation and toxicity of Cd remains unclear. In the present study, we compared the sensitivity to and accumulation of Cd, Mn, and Zn among four types of rat cell lines. Rat basophilic leukemia RBL-2H3 cells showed the highest sensitivity to Cd and Mn due to the highest accumulation of Cd and Mn among the four cell lines. The high accumulation of Cd and Mn was caused by high uptake rates of Cd and Mn. Since relatively high expression of ZIP8 and ZIP14 was found in RBL-2H3 cells, siRNAs of ZIP8 and ZIP14 were transfected into RBL-2H3 cells. The knockdown of ZIP8, but not of ZIP14, significantly reduced the uptake rates of Cd and Mn in RBL-2H3 cells, especially in the presence of bicarbonate. These results suggest that the high expression of ZIP8, which is known to have affinities for both Cd and Mn, resulted in high accumulation of Cd and Mn, leading to high sensitivity to these metals in RBL-2H3 cells. Thus, RBL-2H3 cells may serve as a good model for clarifying the mechanisms of Cd and Mn transport via ZIP8. 相似文献
148.
Genetic analysis of the mode of interplay between an ATPase subunit and membrane subunits of the lipoprotein-releasing ATP-binding cassette transporter LolCDE 下载免费PDF全文
The LolCDE complex, an ATP-binding cassette (ABC) transporter, releases lipoproteins from the inner membrane, thereby initiating lipoprotein sorting to the outer membrane of Escherichia coli. The LolCDE complex is composed of two copies of an ATPase subunit, LolD, and one copy each of integral membrane subunits LolC and LolE. LolD hydrolyzes ATP on the cytoplasmic side of the inner membrane, while LolC and/or LolE recognize and release lipoproteins anchored to the periplasmic leaflet of the inner membrane. Thus, functional interaction between LolD and LolC/E is critically important for coupling of ATP hydrolysis to the lipoprotein release reaction. LolD contains a characteristic sequence called the LolD motif, which is highly conserved among LolD homologs but not other ABC transporters of E. coli. The LolD motif is suggested to be a region in contact with LolC/E, judging from the crystal structures of other ABC transporters. To determine the functions of the LolD motif, we mutagenized each of the 32 residues of the LolD motif and isolated 26 dominant-negative mutants, whose overexpression arrested growth despite the chromosomal lolD(+) background. We then selected suppressor mutations of the lolC and lolE genes that correct the growth defect caused by the LolD mutations. Mutations of the lolC suppressors were mainly located in the periplasmic loop, whereas ones of lolE suppressors were mainly located in the cytoplasmic loop, suggesting that the mode of interaction with LolD differs between LolC and LolE. Moreover, the LolD motif was found to be critical for functional interplay with LolC/E, since some LolD mutations lowered the ATPase activity of LolCDE without affecting that of LolD. 相似文献
149.
Selective acylation of alkyllysophospholipids by docosahexaenoic acid in Ehrlich ascites cells 总被引:1,自引:0,他引:1
Ehrlich ascites cells were cultured with 1-O-[3H]alkylglycero-3-phosphoethanolamine (1-[3H]alkyl-GPE) or 1-O-[3H]alkylglycero-3-phosphocholine (1-[3H]alkyl-GPC) to reveal the selective retention of polyunsaturated fatty acids at second position of ether-containing phospholipids. Although small percentages of the lysophospholipids were degraded into long-chain alcohol, both alkyllyso-GPE and -GPC were acylated at the rate of approximately 2 nmol/30 min per 10(7) cells. Alkylacylacetylglycerols were prepared from the acylated products by phospholipase C treatment, acetylation and TLC, and fractionated according to the degree of unsaturation by AgNO3-TLC. The distribution of the radioactivity among the subfractions indicated that both alkyllysophospholipids were mainly esterified by docosahexaenoic acid and to a somewhat lesser extent by arachidonic acid. The selectivity for docosahexaenoic acid in the esterification of 1-alkyl-GPE was much stronger than in that of 1-alkyl-GPC. Although acyl-CoA: 1-alkyl-glycerophosphoethanolamine acyltransferase activity of Ehrlich cell microsomes with arachidonoyl-CoA and docosahexaenoyl-CoA as acyl donors was negligible compared with the acyl-CoA:1-alkyl-glycerophosphocholine acyltransferase activity, a significant amount of 1-alkyl-GPE was acylated in the microsomes without exogenously added acyl-CoA. HPLC analysis revealed that docosahexaenoic acid and arachidonic acid were mainly esterified by the microsomal transferase. Acylation of 1-alkyl-GPC with docosahexaenoic acid and arachidonic acid was also observed in the absence of added acyl-CoA, but the activity was lower than that for 1-alkyl-GPE. Although the source of the acyl donor in the acylation has not been determined, the acylation is probably due to the direct transfer of acyl groups between intact phospholipids. The above results provided the first evidence that the lysophospholipid acyltransferase system including the transacylase activity participates in the selective retention of docosahexaenoic acid in intact cells and a cell free system. 相似文献
150.
Naito AT Sumida T Nomura S Liu ML Higo T Nakagawa A Okada K Sakai T Hashimoto A Hara Y Shimizu I Zhu W Toko H Katada A Akazawa H Oka T Lee JK Minamino T Nagai T Walsh K Kikuchi A Matsumoto M Botto M Shiojima I Komuro I 《Cell》2012,149(6):1298-1313
Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice, but not in those of C1qa-deficient mice. C1q activates canonical Wnt signaling by binding to Frizzled receptors and subsequently inducing C1s-dependent cleavage of the ectodomain of Wnt coreceptor low-density lipoprotein receptor-related protein 6. Skeletal muscle regeneration in young mice is inhibited by exogenous C1q treatment, whereas aging-associated impairment of muscle regeneration is restored by C1s inhibition or C1qa gene disruption. Our findings therefore suggest the unexpected role of complement C1q in Wnt signal transduction and modulation of mammalian aging. 相似文献