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921.
A Y chromosome census of the British Isles 总被引:7,自引:0,他引:7
Capelli C Redhead N Abernethy JK Gratrix F Wilson JF Moen T Hervig T Richards M Stumpf MP Underhill PA Bradshaw P Shaha A Thomas MG Bradman N Goldstein DB 《Current biology : CB》2003,13(11):979-984
The degree of population replacement in the British Isles associated with cultural changes has been extensively debated. Recent work has demonstrated that comparisons of genetic variation in the British Isles and on the European Continent can illuminate specific demographic processes in the history of the British Isles. For example, Wilson et al. used the similarity of Basque and Celtic Y chromosomes to argue for genetic continuity from the Upper Palaeolithic to the present in the paternal history of these populations (see also ). Differences in the Y chromosome composition of these groups also suggested genetic signatures of Norwegian influence in the Orkney Islands north of the Scottish mainland, an important center of Viking activities between 800 and 1300 A.D. More recently, Weale et al. argued for substantial Anglo-Saxon male migration into central England based on the analysis of eight British sample sets collected on an east-west transect across England and Wales. To provide a more complete assessment of the paternal genetic history of the British Isles, we have compared the Y chromosome composition of multiple geographically distant British sample sets with collections from Norway (two sites), Denmark, and Germany and with collections from central Ireland, representing, respectively, the putative invading and the indigenous populations. By analyzing 1772 Y chromosomes from 25 predominantly small urban locations, we found that different parts of the British Isles have sharply different paternal histories; the degree of population replacement and genetic continuity shows systematic variation across the sampled areas. 相似文献
922.
Jaroch S Hölscher P Rehwinkel H Sülzle D Burton G Hillmann M McDonald FM 《Bioorganic & medicinal chemistry letters》2002,12(18):2561-2564
Dihydroquinolines have been synthesized and have been shown to be potent n-NOS inhibitors. Selectivity versus e-NOS was increased to approximately 100-fold through appropriate substitution at the benzene ring. 相似文献
923.
924.
Regulatory CD4 T cells with the capacity to inhibit potentially harmful immune responses have been described in various experimental systems. Although the observations are converging towards the naturally activated CD25(+) CD4 T cells as a major population responsible for this protection, there is still considerable disagreement on the molecular and cellular requirements involved to achieve a stable immune homeostasis in vivo. 相似文献
925.
Hobbs CJ Bit RA Cansfield AD Harris B Hill CH Hilyard KL Kilford IR Kitas E Kroehn A Lovell P Pole D Rugman P Sherborne BS Smith IE Vesey DR Walmsley DL Whittaker D Williams G Wilson F Banner D Surgenor A Borkakoti N 《Bioorganic & medicinal chemistry letters》2002,12(10):1365-1369
Starting from the tetrapeptide Ac-pYEEI-NHMe and using a structure-based approach, we have designed and synthesised a peptidomimetic ligand for p56(lck) SH2 domain containing a conformationally restricted replacement for the two glutamate residues. We have explored replacments for the isoleucine residue in the pY+3 pocket and thus identified 1-(R)-amino-3-(S)-indaneacetic acid as the most potent replacement. We also report the X-ray crystal structures of two of the antagonists. 相似文献
926.
Carmena M Pinson X Platani M Salloum Z Xu Z Clark A Macisaac F Ogawa H Eggert U Glover DM Archambault V Earnshaw WC 《PLoS biology》2012,10(1):e1001250
The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation. 相似文献
927.
David M. Cross Elizabeth Horsley Mazin Derzi Keith Owen Fiona L. Stavros 《Birth defects research. Part B, Developmental and reproductive toxicology》2012,95(5):327-336
Sitaxentan sodium (Thelin) is a once daily, orally bioavailable, highly selective endothelin A receptor antagonist. Initially approved for the treatment of pulmonary arterial hypertension, sitaxentan was withdrawn in 2010 following the recognition of a pattern of idiosyncratic liver injury. During development of this drug, a series of nonclinical studies investigated the effects of orally administered sitaxentan on fertility, embryofetal development, and pre‐ and postnatal development in the rat; results of these studies are reported here. In the fertility study, sitaxentan did not affect mating behavior, fertility, sperm morphology, or estrous cycle. Sitaxentan was teratogenic in the embyrofetal development study, which was expected based on its pharmacologic mechanism of action. Teratogenic effects included malformations of the head, mouth, face, and large blood vessels. In the pre‐ and postnatal study, sitaxentan administration was associated with reduced pup survival, large or abnormally shaped livers, and delays in markers of auditory and sexual development. Sitaxentan was detected in plasma of suckling pups receiving milk from females dosed with sitaxentan. These nonclinical study findings were reflected in the sitaxentan product label warnings. Birth Defects Res (Part B) 00:1‐10, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
928.
Protein interaction data curation: the International Molecular Exchange (IMEx) consortium 总被引:1,自引:0,他引:1
Orchard S Kerrien S Abbani S Aranda B Bhate J Bidwell S Bridge A Briganti L Brinkman FS Brinkman F Cesareni G Chatr-aryamontri A Chautard E Chen C Dumousseau M Goll J Hancock RE Hancock R Hannick LI Jurisica I Khadake J Lynn DJ Mahadevan U Perfetto L Raghunath A Ricard-Blum S Roechert B Salwinski L Stümpflen V Tyers M Uetz P Xenarios I Hermjakob H 《Nature methods》2012,9(4):345-350
The International Molecular Exchange (IMEx) consortium is an international collaboration between major public interaction data providers to share literature-curation efforts and make a nonredundant set of protein interactions available in a single search interface on a common website (http://www.imexconsortium.org/). Common curation rules have been developed, and a central registry is used to manage the selection of articles to enter into the dataset. We discuss the advantages of such a service to the user, our quality-control measures and our data-distribution practices. 相似文献
929.
930.
Fiona J. McCann Stephen J. Chapman Wai Cho Yu Nick A. Maskell Robert J. O. Davies Y. C. Gary Lee 《PloS one》2012,7(12)
Procalcitonin has been shown to be useful in separating infection from non-infective disorders. However, infection is often paralleled by tissue inflammation. Most studies supporting the use of procalcitonin were confounded by more significant inflammation in the infection group. Few studies have examined the usefulness of procalcitonin when adjusted for inflammation.Pleural inflammation underlies the development of most exudative effusions including pleural infection and malignancy. Pleurodesis, often used to treat effusions, involves provocation of intense aseptic pleural inflammation. We conducted a two-part proof-of-concept study to test the specificity of procalcitonin in differentiating infection using cohorts of patients with pleural effusions of infective and non-infective etiologies, as well as subjects undergoing pleurodesis.