全文获取类型
收费全文 | 1409篇 |
免费 | 175篇 |
出版年
2022年 | 19篇 |
2021年 | 17篇 |
2020年 | 12篇 |
2019年 | 15篇 |
2018年 | 13篇 |
2017年 | 19篇 |
2016年 | 29篇 |
2015年 | 41篇 |
2014年 | 34篇 |
2013年 | 68篇 |
2012年 | 80篇 |
2011年 | 85篇 |
2010年 | 47篇 |
2009年 | 33篇 |
2008年 | 51篇 |
2007年 | 68篇 |
2006年 | 49篇 |
2005年 | 58篇 |
2004年 | 53篇 |
2003年 | 47篇 |
2002年 | 44篇 |
2001年 | 29篇 |
2000年 | 25篇 |
1999年 | 28篇 |
1998年 | 27篇 |
1997年 | 24篇 |
1995年 | 14篇 |
1993年 | 18篇 |
1992年 | 21篇 |
1991年 | 18篇 |
1990年 | 18篇 |
1989年 | 27篇 |
1988年 | 26篇 |
1987年 | 20篇 |
1986年 | 15篇 |
1985年 | 13篇 |
1984年 | 18篇 |
1981年 | 20篇 |
1980年 | 12篇 |
1979年 | 29篇 |
1978年 | 21篇 |
1977年 | 19篇 |
1976年 | 11篇 |
1975年 | 16篇 |
1974年 | 21篇 |
1973年 | 18篇 |
1970年 | 13篇 |
1969年 | 16篇 |
1968年 | 12篇 |
1967年 | 10篇 |
排序方式: 共有1584条查询结果,搜索用时 46 毫秒
991.
Cohn M 《Cellular immunology》2004,227(2):81-92
Arriving at an understanding of the role of suppressor T-cells (regulatory T-cells, CD4(+)CD25+) depends on whether their functional repertoire is somatically selected to be anti-Self or anti-Nonself. Immunologists are ambivalent; often publications espousing opposite views share an author. Here the arguments are detailed that the suppressor repertoire is not somatically selected to be anti-Self, but rather it is anti-Nonself. Therefore, suppression cannot regulate the Self-Nonself discrimination; its function is to regulate the magnitude and class of the anti-Nonself effector response. 相似文献
992.
993.
We report here the genomic organization and phylogenic relationships of CD109, a member of the the alpha2-macroglobulin/complement (AMCOM) gene family. CD109 is a GPI-linked glycoprotein expressed on endothelial cells, platelets, activated T-cells, and a wide variety of tumors. We cloned full-length CD109 cDNA from the mammalian U373 cell line by RT-PCR and performed analysis of its corresponding genomic sequence. The CD109 cDNA spans 128 kb of chromosome 6q with its 33 exons constituting approximately 3.3% of the total CD109 genomic sequence. Sequence analysis revealed that CD109 contains specific motifs in its N-terminus, that are highly conserved in all AMCOM members. CD109 also shares motifs with certain other AMCOM members including: (1) a thioester 'GCGEQ" motif, (2) a furin site of four positively charged amino acids, and (3) a double tyrosine near the C-terminus. Based on a phylogenic analysis of human CD109 with other human homologs as well as orthologs from other mammalian species, C. elegans (ZK337.1) and E. coli homologs, we propose CD109 represents a novel and independent branch of the alpha2-macroglobulin/complement gene family (AMCOM) and may be its oldest member. 相似文献
994.
Previous studies have shown that p34(SEI-1), also known as TRIP-Br1, is involved in cell cycle regulations by interacting with a number of important proteins including CDK4. However, the detailed mechanism and structural basis of the interaction remains to be determined. We report the use of in vitro studies to address these problems. First, it was shown that p34(SEI-1) binds to CDK4 directly, and the binding does not compete directly with p16. In the presence of p16, a quaternary complex is formed between p34(SEI-1), CDK4, cyclin D2, and p16. Second, it was found that p34(SEI-1) activates the kinase activity of CDK4 at lower concentrations (reaching the maximum at 500 nM) but inhibits the same activity at higher concentrations, implying that p34(SEI-1)-mediated CDK4 activation is dose-dependent. Again, the effects of p34(SEI-1) and p16 are independent of each other. Third, it was shown that p34(SEI-1) possesses a LexA-mediated transactivation activity. Finally, a set of truncation mutants were used to dissect the structural elements responsible for the different functions of p34(SEI-1). The results indicate that the fragment 30-160 can bind, activate, and inhibit CDK4; the fragment 30-132 can bind and activate but does not inhibit CDK4, while the fragment 30-88 cannot bind, activate, or inhibit but retains the LexA-mediated transactivation activity. 相似文献
995.
Pepper AS McCane JE Kemper K Yeung DA Lee RC Ambros V Moss EG 《Development (Cambridge, England)》2004,131(9):2049-2059
The succession of developmental events in the C. elegans larva is governed by the heterochronic genes. When mutated, these genes cause either precocious or retarded developmental phenotypes, in which stage-specific patterns of cell division and differentiation are either skipped or reiterated, respectively. We identified a new heterochronic gene, lin-46, from mutations that suppress the precocious phenotypes caused by mutations in the heterochronic genes lin-14 and lin-28. lin-46 mutants on their own display retarded phenotypes in which cell division patterns are reiterated and differentiation is prevented in certain cell lineages. Our analysis indicates that lin-46 acts at a step immediately downstream of lin-28, affecting both the regulation of the heterochronic gene pathway and execution of stage-specific developmental events at two stages: the third larval stage and adult. We also show that lin-46 is required prior to the third stage for normal adult cell fates, suggesting that it acts once to control fates at both stages, and that it affects adult fates through the let-7 branch of the heterochronic pathway. Interestingly, lin-46 encodes a protein homologous to MoeA of bacteria and the C-terminal domain of mammalian gephyrin, a multifunctional scaffolding protein. Our findings suggest that the LIN-46 protein acts as a scaffold for a multiprotein assembly that controls developmental timing, and expand the known roles of gephyrin-related proteins to development. 相似文献
996.
Genome scan meta-analysis of schizophrenia and bipolar disorder,part III: Bipolar disorder 总被引:13,自引:3,他引:10
Segurado R Detera-Wadleigh SD Levinson DF Lewis CM Gill M Nurnberger JI Craddock N DePaulo JR Baron M Gershon ES Ekholm J Cichon S Turecki G Claes S Kelsoe JR Schofield PR Badenhop RF Morissette J Coon H Blackwood D McInnes LA Foroud T Edenberg HJ Reich T Rice JP Goate A McInnis MG McMahon FJ Badner JA Goldin LR Bennett P Willour VL Zandi PP Liu J Gilliam C Juo SH Berrettini WH Yoshikawa T Peltonen L Lönnqvist J Nöthen MM Schumacher J Windemuth C Rietschel M Propping P Maier W Alda M Grof P 《American journal of human genetics》2003,73(1):49-62
Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for “very narrow” (i.e., BP-I and schizoaffective disorder–BP) and “narrow” (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A “broad” model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region. 相似文献
997.
HLA genes in the Chuvashian population from European Russia: admixture of Central European and Mediterranean populations 总被引:3,自引:0,他引:3
Arnaiz-Villena A Martinez-Laso J Moscoso J Livshits G Zamora J Gomez-Casado E Silvera-Redondo C Melvin K Crawford MH 《Human biology; an international record of research》2003,75(3):375-392
HLA alleles have been determined for the first time in individuals from the Chuvashian population by DNA typing and sequencing. HLA-A, -B, -DR, and -DQ allele frequencies and extended haplotypes have also been determined, and the results compared to those for Central Europeans, Siberians and other Asians, Caucasians, Middle Easterners, and Mediterranean peoples. Genetic distances, neighbor-joining dendrograms, and correspondence analysis have been performed. Present-day Chuvash speak an Altaic-Turkic language and are genetically related to Caucasians (Georgians), Mediterraneans, and Middle Easterners, and not only to Central or Northern Europeans; Chuvash contain little indications of Central Asian-Altaic gene flow. Thus, present-day Chuvash who speak an Altaic-Turkic language are probably more closely related to ancient Mesopotamian-Hittites and northern European populations than to central Asia-Altaic people. 相似文献
998.
Cohn M 《Cellular immunology》2003,221(2):138-142
The immune system somatically generates a large and random paratopic repertoire that must be sorted into those specificities (anti-self) which, if expressed, would debilitate the host and those specificities (anti-nonself) which, if not expressed, would leave the host unprotected from infection. The critique of Efroni and Cohen that minimal models are misleading and without heuristic value is evaluated by illustrative examples. 相似文献
999.
Multiple viral genetic analyses detect low-level human immunodeficiency virus type 1 replication during effective highly active antiretroviral therapy
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Frenkel LM Wang Y Learn GH McKernan JL Ellis GM Mohan KM Holte SE De Vange SM Pawluk DM Melvin AJ Lewis PF Heath LM Beck IA Mahalanabis M Naugler WE Tobin NH Mullins JI 《Journal of virology》2003,77(10):5721-5730
To evaluate human immunodeficiency virus type 1 (HIV-1) replication and selection of drug-resistant viruses during seemingly effective highly active antiretroviral therapy (HAART), multiple HIV-1 env and pol sequences were analyzed and viral DNA levels were quantified from nucleoside analog-experienced children prior to and during a median of 5.1 (range, 1.8 to 6.4) years of HAART. Viral replication was detected at different rates, with apparently increasing sensitivity: 1 of 10 by phylogenetic analysis; 2 of 10 by viral evolution with increasing genetic distances from the most recent common ancestor (MRCA) of infection; 3 of 10 by selection of drug-resistant mutants; and 6 of 10 by maintenance of genetic distances from the MRCA. When four- or five-drug antiretroviral regimens were given to these children, persistent plasma viral rebound did not occur despite the accumulation of highly drug-resistant genotypes. Among the four children without genetic evidence of viral replication, a statistically significant decrease in the genetic distance to the MRCA was detected in three, indicating the persistence of a greater number of early compared to recent viruses, and their HIV-1 DNA decreased by > or =0.9 log(10), resulting in lower absolute DNA levels (P = 0.007). This study demonstrates the variable rates of viral replication when HAART has suppressed plasma HIV-1 RNA for years to a median of <50 copies/ml and that combinations of four or five antiretroviral drugs suppress viral replication even after short-term virologic failure of three-drug HAART and despite ongoing accumulation of drug-resistant mutants. Furthermore, the decrease of cellular HIV-1 DNA to low absolute levels in those without genetic evidence of viral replication suggests that monitoring viral DNA during HAART may gauge low-level replication. 相似文献
1000.
DePamphilis ML 《Cell》2003,114(3):274-275