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351.
Potter BA Irish JD Reuther JD Gelvin-Reymiller C Holliday VT 《Science (New York, N.Y.)》2011,331(6020):1058-1062
The dearth of human remains and residential sites has constrained inquiry into Beringian lifeways at the transition of the late Pleistocene-early Holocene. We report on human skeletal remains and a residential structure from central Alaska dated to ~11,500 calendar years ago. The remains are from a ~3-year-old child who was cremated in a pit within a semisubterranean house. The burial-cremation and house have exceptional integrity and preservation and exhibit similarities and differences to both Siberian Upper Paleolithic and North American Paleoindian features. 相似文献
352.
Berrettini W Bierut L Crowley TJ Cubells JF Frascella J Gelernter J Hewitt JK Kreek MJ Lachman H Leppert M Li MD Madden P Miner C Pollock JD Pomerleau O Rice JP Rutter JL Shurtleff D Swan GE Tischfield JA Tsuang M Uhl GR Vanyukov M Volkow ND Wanke K 《Science (New York, N.Y.)》2004,304(5676):1445-7; author reply 1445-7
353.
Heisler LK Cowley MA Tecott LH Fan W Low MJ Smart JL Rubinstein M Tatro JB Marcus JN Holstege H Lee CE Cone RD Elmquist JK 《Science (New York, N.Y.)》2002,297(5581):609-611
D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients. Discerning the neurobiology underlying the anorexic action of d-FEN may facilitate the development of new drugs to prevent and treat obesity. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we show that d-FEN-induced anorexia requires activation of central nervous system melanocortin pathways. These results provide a mechanistic explanation of d-FEN's anorexic actions and indicate that drugs targeting these downstream melanocortin pathways may prove to be effective and more selective anti-obesity treatments. 相似文献
354.
Early specification of endomesodermal territories in the sea urchin embryo depends on a moving torus of regulatory gene expression. We show how this dynamic patterning function is encoded in a gene regulatory network (GRN) subcircuit that includes the otx, wnt8, and blimp1 genes, the cis-regulatory control systems of which have all been experimentally defined. A cis-regulatory reconstruction experiment revealed that blimp1 autorepression accounts for progressive extinction of expression in the center of the torus, whereas its outward expansion follows reception of the Wnt8 ligand by adjacent cells. GRN circuitry thus controls not only static spatial assignment in development but also dynamic regulatory patterning. 相似文献
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357.
Diabetes Genetics Initiative of Broad Institute of Harvard MIT Lund University Novartis Institutes of BioMedical Research Saxena R Voight BF Lyssenko V Burtt NP de Bakker PI Chen H Roix JJ Kathiresan S Hirschhorn JN Daly MJ Hughes TE Groop L Altshuler D Almgren P Florez JC Meyer J Ardlie K Bengtsson Boström K Isomaa B Lettre G Lindblad U Lyon HN Melander O Newton-Cheh C Nilsson P Orho-Melander M Råstam L Speliotes EK Taskinen MR Tuomi T Guiducci C Berglund A Carlson J Gianniny L 《Science (New York, N.Y.)》2007,316(5829):1331-1336
New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases. 相似文献
358.
Hanotte O Bradley DG Ochieng JW Verjee Y Hill EW Rege JE 《Science (New York, N.Y.)》2002,296(5566):336-339
The genetic history of African cattle pastoralism is controversial and poorly understood. We reveal the genetic signatures of its origins, secondary movements, and differentiation through the study of 15 microsatellite loci in 50 indigenous cattle breeds spanning the present cattle distribution in Africa. The earliest cattle originated within the African continent, but Near East and European genetic influences are also identified. The initial expansion of African Bos taurus was likely from a single region of origin. It reached the southern part of the continent by following an eastern route rather than a western one. The B. indicus genetic influence shows a major entry point through the Horn and the East Coast of Africa and two modes of introgression into the continent. 相似文献
359.
Bertone P Stolc V Royce TE Rozowsky JS Urban AE Zhu X Rinn JL Tongprasit W Samanta M Weissman S Gerstein M Snyder M 《Science (New York, N.Y.)》2004,306(5705):2242-2246
Elucidating the transcribed regions of the genome constitutes a fundamental aspect of human biology, yet this remains an outstanding problem. To comprehensively identify coding sequences, we constructed a series of high-density oligonucleotide tiling arrays representing sense and antisense strands of the entire nonrepetitive sequence of the human genome. Transcribed sequences were located across the genome via hybridization to complementary DNA samples, reverse-transcribed from polyadenylated RNA obtained from human liver tissue. In addition to identifying many known and predicted genes, we found 10,595 transcribed sequences not detected by other methods. A large fraction of these are located in intergenic regions distal from previously annotated genes and exhibit significant homology to other mammalian proteins. 相似文献