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951.
Bartos JD Gaile DP McQuaid DE Conroy JM Darbary H Nowak NJ Block A Petrelli NJ Mittelman A Stoler DL Anderson GR 《Mutation research》2007,615(1-2):1-11
In order to identify small regions of the genome whose specific copy number alteration is associated with high genomic instability in the form of overall genome-wide copy number aberrations, we have analyzed array-based comparative genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy number changes of a small number of specific regions were significantly correlated with elevated overall amplifications and deletions scattered throughout the entire genome. One significant region at 9q34 includes the c-ABL gene. Another region spanning 22q11-q13 includes the breakpoint cluster region (BCR) of the Philadelphia chromosome. Coordinate 22q11-q13 alterations were observed in 9 of 11 tumors with the 9q34 alteration. Additional regions on 1q and 14q were associated with overall genome-wide copy number changes, while copy number aberrations on chromosome 7p, 7q, and 13q21.1-q31.3 were found associated with this instability only in tumors from patients with a smoking history. Our analysis demonstrates there are a small number of regions of the genome where gain or loss is commonly associated with a tumor's overall level of copy number aberrations. Our finding BCR and ABL located within two of the instability-associated regions, and the involvement of these two regions occurring coordinately, suggests a system akin to the BCR-ABL translocation of CML may be involved in genomic instability in about one-third of human colorectal carcinomas. 相似文献
952.
953.
Myiasis is the infestation of live human and vertebrate animals with dipterous larvae which, at least for a short period, feed on the host's dead or living tissue, liquid body-substance, or ingested food. The objective of this study was to identify the flies producing myiasis in Bahía Blanca city, Argentina, from 01/03/2000 to 31/05/2005. Seventeen clinical cases were studied. The larvae obtained from lesions were forwarded from laboratories and from public and private hospitals. Part of the larvae were fixed in alcohol 70 masculine and processed according to the Mazza & J?rg technique (1939). The other part continued growing in flasks with meat in laboratory conditions to obtain the adults. The etiological agents of myiasis were identified by observing the diagnostic characteristics of the larvae III and of the adults, and by using taxonomic keys. Myiasis was produced by Cochlyiomia hominivorax (Coquerel) in thirteen of the cases and by Phaenicia sericata (= Lucila sericata) (Meigen) (Diptera: Calliphoridae) in the other four. The cases were traumatic and aural myiasis and happened from December to March. The ages of patients were four to eighty-six years and 76.5% of the cases occurred in male patients. Given the aggressiveness of these larvae, mainly C. hominivorax, in causing human myiasis, the importance of specific and quick diagnosis and of adequate treatment must be acknowledged. 相似文献
954.
The cell wall of Candida albicans lies at the crossroads of pathogenicity and therapeutics. It contributes to pathogenicity through adherence and invasion; it is the target of both chemical and immunological antifungal strategies. We have initiated a dissection of cell wall function through targeted insertional mutagenesis of cell wall-related genes. Among 25 such genes, we were unable to generate homozygous mutations in 4, and they may be essential for viability. We created homozygous mutations in the remaining 21 genes. Insertion mutations in SUN41, Orf19.5412, Orf19.1277, MSB2, Orf19.3869, and WSC1 caused hypersensitivity to the cell wall inhibitor caspofungin, while two different ecm33 insertions caused mild caspofungin resistance. Insertion mutations in SUN41 and Orf19.5412 caused biofilm defects. Through analysis of homozygous sun41Delta/sun41Delta deletion mutants and sun41Delta/sun41Delta+pSUN41-complemented strains, we verified that Sun41 is required for biofilm formation and normal caspofungin tolerance. The sun41Delta/sun41Delta mutant had altered expression of four cell wall damage response genes, thus suggesting that it suffers a cell wall structural defect. Sun41 is required for inducing disease, because the mutant was severely attenuated in mouse models of disseminated and oropharyngeal candidiasis. Although the mutant produced aberrant hyphae, it had no defect in damaging endothelial or epithelial cells, unlike many other hypha-defective mutants. We suggest that the sun41Delta/sun41Delta cell wall defect is the primary cause of its attenuated virulence. As a small fungal surface protein with predicted glucosidase activity, Sun41 represents a promising therapeutic target. 相似文献
955.
Miliaras D Conroy J Pervana S Meditskou S McQuaid D Nowak N 《Birth defects research. Part A, Clinical and molecular teratology》2007,79(3):236-241
BACKGROUND: Placental hemangioma (chorioangioma) and congenital hemangioma are relatively common tumors, which on rare occasions may occur together. Very little is known about the pathogenetic mechanisms underlying these lesions. CASE: Herein we describe a rare case of a stillborn infant with chorioangioma, placental mesenchymal dysplasia, and liver cavernous hemangioma. In addition, we present the findings of the karyotype analysis of these lesions, which was done with the bacterial artificial chromosome arrays using the comparative genomic hybridization method. The chromosomal abnormalities that we found were deletions at 2q13 and 7p21.1 and were common to both placental and liver lesions. CONCLUSIONS: None of the identified chromosomal aberrations have been previously associated with chorioangiomas or hemangiomas. Important genes that lie in these DNA regions may be implicated in the pathogenesis of congenital hemangiomas and mesenchymal dysplasia. 相似文献
956.
Elise Buisson Soizig Le Stradic Fernando A. O. Silveira Giselda Durigan Gerhard E. Overbeck Alessandra Fidelis G. Wilson Fernandes William J. Bond Julia‐Maria Hermann Gregory Mahy Swanni T. Alvarado Nicholas P. Zaloumis Joseph W. Veldman 《Biological reviews of the Cambridge Philosophical Society》2019,94(2):590-609
Despite growing recognition of the conservation values of grassy biomes, our understanding of how to maintain and restore biodiverse tropical grasslands (including savannas and open‐canopy grassy woodlands) remains limited. To incorporate grasslands into large‐scale restoration efforts, we synthesised existing ecological knowledge of tropical grassland resilience and approaches to plant community restoration. Tropical grassland plant communities are resilient to, and often dependent on, the endogenous disturbances with which they evolved – frequent fires and native megafaunal herbivory. In stark contrast, tropical grasslands are extremely vulnerable to human‐caused exogenous disturbances, particularly those that alter soils and destroy belowground biomass (e.g. tillage agriculture, surface mining); tropical grassland restoration after severe soil disturbances is expensive and rarely achieves management targets. Where grasslands have been degraded by altered disturbance regimes (e.g. fire exclusion), exotic plant invasions, or afforestation, restoration efforts can recreate vegetation structure (i.e. historical tree density and herbaceous ground cover), but species‐diverse plant communities, including endemic species, are slow to recover. Complicating plant‐community restoration efforts, many tropical grassland species, particularly those that invest in underground storage organs, are difficult to propagate and re‐establish. To guide restoration decisions, we draw on the old‐growth grassland concept, the novel ecosystem concept, and theory regarding tree cover along resource gradients in savannas to propose a conceptual framework that classifies tropical grasslands into three broad ecosystem states. These states are: (1) old‐growth grasslands (i.e. ancient, biodiverse grassy ecosystems), where management should focus on the maintenance of disturbance regimes; (2) hybrid grasslands, where restoration should emphasise a return towards the old‐growth state; and (3) novel ecosystems, where the magnitude of environmental change (i.e. a shift to an alternative ecosystem state) or the socioecological context preclude a return to historical conditions. 相似文献
957.
Improved Detection of Citrus psorosis virus and Coat Protein‐Derived Transgenes in Citrus Plants: Comparison Between RT‐qPCR and TAS‐ELISA 下载免费PDF全文
Agustina De Francesco Norma Costa María I. Plata María L. García 《Journal of Phytopathology》2015,163(11-12):915-925
Citrus is one of the most economically important fruit crops in the world. Citrus psorosis is a serious disease affecting mainly oranges and mandarins in Argentina and Uruguay. The causal agent is Citrus psorosis virus (CPsV), an ophiovirus with a tripartite ssRNA genome of negative polarity. The coat protein (CP), the most abundant viral protein in infected plants, has been used to detect CPsV by TAS‐ELISA, but only biological indexing, requiring 1 year, is the current and validated technique for diagnosis of citrus psorosis. In this study, a SYBR Green RT‐qPCR protocol was developed, with primers designed to the most conserved region of the cp gene. We tested their specificity and sensitivity in comparison with TAS‐ELISA. This RT‐qPCR was applied successfully to field samples from Argentina, to a variety of isolates from different countries maintained in the greenhouse, to young seedlings and old trees from a psorosis natural transmission plot, and to transgenic citrus expressing the cp gene of CPsV or a fragment thereof. This method allowed accurate quantification of viral titer and cp gene expression in transgenic plants, which could not be detected previously. The sensitivity and reliability of quantitative CPsV detection were improved with greater speed using commercial reagents, and the sensitivity was three orders of magnitude higher than that of TAS‐ELISA. All these data encourage its validation. 相似文献
958.
Marta Marin‐Argany Jofre Güell‐Bosch Luis M. Blancas‐Mejía Sandra Villegas Marina Ramirez‐Alvarado 《Protein science : a publication of the Protein Society》2015,24(11):1829-1840
Light chain (AL) amyloidosis is an incurable human disease, where the amyloid precursor is a misfolding‐prone immunoglobulin light‐chain. Here, we identify the role of somatic mutations in the structure, stability and in vitro fibril formation for an amyloidogenic AL‐12 protein by restoring four nonconservative mutations to their germline (wild‐type) sequence. The single restorative mutations do not affect significantly the native structure, the unfolding pathway, and the reversibility of the protein. However, certain mutations either decrease (H32Y and H70D) or increase (R65S and Q96Y) the protein thermal stability. Interestingly, the most and the least stable mutants, Q96Y and H32Y, do not form amyloid fibrils under physiological conditions. Thus, Q96 and H32 are key residues for AL‐12 stability and fibril formation and restoring them to the wild‐type residues preclude amyloid formation. The mutants whose equilibrium is shifted to either the native or unfolded states barely sample transient partially folded states, and therefore do not form fibrils. These results agree with previous observations by our laboratory and others that amyloid formation occurs because of the sampling of partially folded states found within the unfolding transition (Blancas‐Mejia and Ramirez‐Alvarado, Ann Rev Biochem 2013;82:745–774). Here we provide a new insight on the AL amyloidosis mechanism by demonstrating that AL‐12 does not follow the established thermodynamic hypothesis of amyloid formation. In this hypothesis, thermodynamically unstable proteins are more prone to amyloid formation. Here we show that within a thermal stability range, the most stable protein in this study is the most amyloidogenic protein. 相似文献
959.
Rafik Salama Norma Masson Peter Simpson Lina Katrin Sciesielski Min Sun Ya-Min Tian Peter John Ratcliffe David Robert Mole 《PloS one》2015,10(8)
General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1α and HIF-2α have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1α and HIF-2α and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1α-specific binding, and genes associated with favorable prognosis and between HIF-2α-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-α isoform contributes a highly complex mix of pro- and anti-tumorigenic effects. 相似文献
960.
Asymmetric Nerve Enlargement: A Characteristic of Leprosy Neuropathy Demonstrated by Ultrasonography
Helena Barbosa Lug?o Marcello Henrique Nogueira-Barbosa Wilson Marques Jr. Norma Tiraboschi Foss Marco Andrey Cipriani Frade 《PLoS neglected tropical diseases》2015,9(12)