全文获取类型
收费全文 | 18884篇 |
免费 | 103篇 |
国内免费 | 234篇 |
专业分类
系统科学 | 398篇 |
丛书文集 | 383篇 |
教育与普及 | 78篇 |
理论与方法论 | 75篇 |
现状及发展 | 6355篇 |
研究方法 | 917篇 |
综合类 | 10397篇 |
自然研究 | 618篇 |
出版年
2014年 | 154篇 |
2013年 | 293篇 |
2012年 | 551篇 |
2011年 | 1185篇 |
2010年 | 394篇 |
2009年 | 348篇 |
2008年 | 591篇 |
2007年 | 688篇 |
2006年 | 681篇 |
2005年 | 616篇 |
2004年 | 474篇 |
2003年 | 374篇 |
2002年 | 379篇 |
2001年 | 512篇 |
2000年 | 560篇 |
1999年 | 413篇 |
1992年 | 292篇 |
1991年 | 253篇 |
1990年 | 254篇 |
1989年 | 230篇 |
1988年 | 213篇 |
1987年 | 228篇 |
1986年 | 204篇 |
1985年 | 246篇 |
1984年 | 240篇 |
1983年 | 163篇 |
1982年 | 174篇 |
1981年 | 157篇 |
1980年 | 199篇 |
1979年 | 446篇 |
1978年 | 345篇 |
1977年 | 368篇 |
1976年 | 267篇 |
1975年 | 322篇 |
1974年 | 447篇 |
1973年 | 380篇 |
1972年 | 364篇 |
1971年 | 425篇 |
1970年 | 486篇 |
1969年 | 430篇 |
1968年 | 409篇 |
1967年 | 444篇 |
1966年 | 385篇 |
1965年 | 302篇 |
1959年 | 155篇 |
1958年 | 232篇 |
1957年 | 179篇 |
1956年 | 138篇 |
1955年 | 154篇 |
1954年 | 132篇 |
排序方式: 共有10000条查询结果,搜索用时 640 毫秒
971.
972.
Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus 总被引:22,自引:0,他引:22
Hong YK Foreman K Shin JW Hirakawa S Curry CL Sage DR Libermann T Dezube BJ Fingeroth JD Detmar M 《Nature genetics》2004,36(7):683-685
Kaposi sarcoma is considered a neoplasm of lymphatic endothelium infected with Kaposi sarcoma-associated herpesvirus. It is characterized by the expression of lymphatic lineage-specific genes by Kaposi sarcoma tumor cells. Here we show that infection of differentiated blood vascular endothelial cells with Kaposi sarcoma-associated herpesvirus leads to their lymphatic reprogramming; induction of approximately 70% of the main lymphatic lineage-specific genes, including PROX1, a master regulator of lymphatic development; and downregulation of blood vascular genes. 相似文献
973.
Ding H Wu X Boström H Kim I Wong N Tsoi B O'Rourke M Koh GY Soriano P Betsholtz C Hart TC Marazita ML Field LL Tam PP Nagy A 《Nature genetics》2004,36(10):1111-1116
PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This phenotype was less severe than that of Pdgfra(-/-) embryos. Pdgfc(-/-) Pdgfa(-/-) embryos developed a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects. Complete loss of function of both ligands, therefore, phenocopied the loss of PDGFR-alpha function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-alpha to regulate the development of craniofacial structures, the neural tube and mesodermal organs. Our results also show that PDGF-C signaling is a new pathway in palatogenesis, different from, and independent of, those previously implicated. 相似文献
974.
Krantz ID McCallum J DeScipio C Kaur M Gillis LA Yaeger D Jukofsky L Wasserman N Bottani A Morris CA Nowaczyk MJ Toriello H Bamshad MJ Carey JC Rappaport E Kawauchi S Lander AD Calof AL Li HH Devoto M Jackson LG 《Nature genetics》2004,36(6):631-635
Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited multisystem developmental disorder characterized by growth and cognitive retardation; abnormalities of the upper limbs; gastroesophageal dysfunction; cardiac, ophthalmologic and genitourinary anomalies; hirsutism; and characteristic facial features. Genital anomalies, pyloric stenosis, congenital diaphragmatic hernias, cardiac septal defects, hearing loss and autistic and self-injurious tendencies also frequently occur. Prevalence is estimated to be as high as 1 in 10,000 (ref. 4). We carried out genome-wide linkage exclusion analysis in 12 families with CdLS and identified four candidate regions, of which chromosome 5p13.1 gave the highest multipoint lod score of 2.7. This information, together with the previous identification of a child with CdLS with a de novo t(5;13)(p13.1;q12.1) translocation, allowed delineation of a 1.1-Mb critical region on chromosome 5 for the gene mutated in CdLS. We identified mutations in one gene in this region, which we named NIPBL, in four sporadic and two familial cases of CdLS. We characterized the genomic structure of NIPBL and found that it is widely expressed in fetal and adult tissues. The fly homolog of NIPBL, Nipped-B, facilitates enhancer-promoter communication and regulates Notch signaling and other developmental pathways in Drosophila melanogaster. 相似文献
975.
Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia 总被引:16,自引:0,他引:16
Hu Y Liu Y Pelletier S Buchdunger E Warmuth M Fabbro D Hallek M Van Etten RA Li S 《Nature genetics》2004,36(5):453-461
The Abl kinase inhibitor imatinib mesylate is the preferred treatment for Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) in chronic phase but is much less effective in CML blast crisis or Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). Here, we show that Bcr-Abl activated the Src kinases Lyn, Hck and Fgr in B-lymphoid cells. BCR-ABL1 retrovirus-transduced marrow from mice lacking all three Src kinases efficiently induced CML but not B-ALL in recipients. The kinase inhibitor CGP76030 impaired the proliferation of B-lymphoid cells expressing Bcr-Abl in vitro and prolonged survival of mice with B-ALL but not CML. The combination of CGP76030 and imatinib was superior to imatinib alone in this regard. The biochemical target of CGP76030 in leukemia cells was Src kinases, not Bcr-Abl. These results implicate Src family kinases as therapeutic targets in Ph(+) B-ALL and suggest that simultaneous inhibition of Src and Bcr-Abl kinases may benefit individuals with Ph(+) acute leukemia. 相似文献
976.
977.
Now that some genomes have been completely sequenced, the ability to direct specific mutations into genomes is particularly desirable. Here we present a method to create mutations in the Caenorhabditis elegans genome efficiently through transgene-directed, transposon-mediated gene conversion. Engineered deletions targeted into two genes show that the frequency of obtaining the desired mutation was higher using this approach than using standard transposon insertion-deletion approaches. We also targeted an engineered green fluorescent protein insertion-replacement cassette to one of these genes, thereby confirming that custom alleles of different types can be created in vitro to make the corresponding mutations in vivo. This approach should also be applicable to heterologous transposons in C. elegans and other organisms, including vertebrates. 相似文献
978.
Léveillard T Mohand-Saïd S Lorentz O Hicks D Fintz AC Clérin E Simonutti M Forster V Cavusoglu N Chalmel F Dollé P Poch O Lambrou G Sahel JA 《Nature genetics》2004,36(7):755-759
Retinitis pigmentosa is an untreatable, inherited retinal disease that leads to blindness. The disease initiates with the loss of night vision due to rod photoreceptor degeneration, followed by irreversible, progressive loss of cone photoreceptor. Cone loss is responsible for the main visual handicap, as cones are essential for day and high-acuity vision. Their loss is indirect, as most genes associated with retinitis pigmentosa are not expressed by these cells. We previously showed that factors secreted from rods are essential for cone viability. Here we identified one such trophic factor by expression cloning and named it rod-derived cone viability factor (RdCVF). RdCVF is a truncated thioredoxin-like protein specifically expressed by photoreceptors. The identification of this protein offers new treatment possibilities for retinitis pigmentosa. 相似文献
979.
The knockout mouse project 总被引:1,自引:0,他引:1
Austin CP Battey JF Bradley A Bucan M Capecchi M Collins FS Dove WF Duyk G Dymecki S Eppig JT Grieder FB Heintz N Hicks G Insel TR Joyner A Koller BH Lloyd KC Magnuson T Moore MW Nagy A Pollock JD Roses AD Sands AT Seed B Skarnes WC Snoddy J Soriano P Stewart DJ Stewart F Stillman B Varmus H Varticovski L Verma IM Vogt TF von Melchner H Witkowski J Woychik RP Wurst W Yancopoulos GD Young SG Zambrowicz B 《Nature genetics》2004,36(9):921-924
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. 相似文献
980.