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921.
Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts 总被引:14,自引:0,他引:14
Cohen AW Park DS Woodman SE Williams TM Chandra M Shirani J Pereira de Souza A Kitsis RN Russell RG Weiss LM Tang B Jelicks LA Factor SM Shtutin V Tanowitz HB Lisanti MP 《American journal of physiology. Cell physiology》2003,284(2):C457-C474
Recently, development ofa caveolin-1-deficient (Cav-1 null) mouse model has allowed thedetailed analysis of caveolin-1's function in the context of awhole animal. Interestingly, we now report that the hearts ofCav-1 null mice are markedly abnormal, despite the fact that caveolin-1is not expressed in cardiac myocytes. However, caveolin-1 is abundantlyexpressed in the nonmyocytic cells of the heart, i.e., cardiacfibroblasts and endothelia. Quantitative imaging studies of Cav-1 nullhearts demonstrate a significantly enlarged right ventricular cavityand a thickened left ventricular wall with decreased systolic function.Histological analysis reveals myocyte hypertrophy withinterstitial/perivascular fibrosis. Because caveolin-1 is thought toact as a negative regulator of the p42/44 MAP kinase cascade, weperformed Western blot analysis with phospho-specific antibodies thatonly recognize activated ERK1/2. As predicted, the p42/44 MAP kinasecascade is hyperactivated in Cav-1 null heart tissue (i.e.,interstitial fibrotic lesions) and isolated cardiac fibroblasts. Inaddition, endothelial and inducible nitric oxide synthase levels aredramatically upregulated. Thus loss of caveolin-1 expression drivesp42/44 MAP kinase activation and cardiac hypertrophy. 相似文献
922.
Martin F. Breed Michael G. Stead Kym M. Ottewell Michael G. Gardner Andrew J. Lowe 《Conservation Genetics》2013,14(1):1-10
Revegetation is one practical application of science that should ideally aim to combine ecology with evolution to maximise biodiversity and ecosystem outcomes. The strict use of locally sourced seed in revegetation programs is widespread and is based on the expectation that populations are locally adapted. This practice does not fully integrate two global drivers of ecosystem change and biodiversity loss: habitat fragmentation and climate change. Here, we suggest amendments to existing strategies combined with a review of alternative seed-sourcing strategies that propose to mitigate against these drivers. We present a provenancing selection guide based on confidence surrounding climate change distribution modelling and data on population genetic and/or environmental differences between populations. Revegetation practices will benefit from greater integration of current scientific developments and establishment of more long-term experiments is key to improving the long-term success. The rapid growth in carbon and biodiversity markets creates a favourable economic climate to achieve these outcomes. 相似文献
923.
Matthew R. Evans Mike Bithell Stephen J. Cornell Sasha R. X. Dall Sandra Díaz Stephen Emmott Bruno Ernande Volker Grimm David J. Hodgson Simon L. Lewis Georgina M. Mace Michael Morecroft Aristides Moustakas Eugene Murphy Tim Newbold K. J. Norris Owen Petchey Matthew Smith Justin M. J. Travis Tim G. Benton 《Proceedings. Biological sciences / The Royal Society》2013,280(1771)
Human societies, and their well-being, depend to a significant extent on the state of the ecosystems that surround them. These ecosystems are changing rapidly usually in response to anthropogenic changes in the environment. To determine the likely impact of environmental change on ecosystems and the best ways to manage them, it would be desirable to be able to predict their future states. We present a proposal to develop the paradigm of predictive systems ecology, explicitly to understand and predict the properties and behaviour of ecological systems. We discuss the necessary and desirable features of predictive systems ecology models. There are places where predictive systems ecology is already being practised and we summarize a range of terrestrial and marine examples. Significant challenges remain but we suggest that ecology would benefit both as a scientific discipline and increase its impact in society if it were to embrace the need to become more predictive. 相似文献
924.
Shirley M. H. Sy Jun Jiang Wai Sum O Yiqun Deng Michael S. Y. Huen 《Nucleic acids research》2013,41(18):8572-8580
Ubiquitylation plays key roles in DNA damage signal transduction. The current model envisions that lysine63-linked ubiquitin chains, via the concerted action of E3 ubiquitin ligases RNF8-RNF168, are built at DNA double-strand breaks (DSBs) to effectively assemble DNA damage-repair factors for proper checkpoint control and DNA repair. We found that RNF168 is a short-lived protein that is stabilized by the deubiquitylating enzyme USP34 in response to DNA damage. In the absence of USP34, RNF168 is rapidly degraded, resulting in attenuated DSB-associated ubiquitylation, defective recruitment of BRCA1 and 53BP1 and compromised cell survival after ionizing radiation. We propose that USP34 promotes a feed-forward loop to enforce ubiquitin signaling at DSBs and highlight critical roles of ubiquitin dynamics in genome stability maintenance. 相似文献
925.
Peter D. Burbelo Kathryn H. Ching Caryn G. Morse Ilias Alevizos Ahmad Bayat Jeffrey I. Cohen Mir A. Ali Amit Kapoor Sarah K. Browne Steven M. Holland Joseph A. Kovacs Michael J. Iadarola 《PloS one》2013,8(12)
Despite the important diagnostic value of evaluating antibody responses to individual human pathogens, antibody profiles against multiple infectious agents have not been used to explore health and disease mainly for technical reasons. We hypothesized that the interplay between infection and chronic disease might be revealed by profiling antibodies against multiple agents. Here, the levels of antibodies against a panel of 13 common infectious agents were evaluated with the quantitative Luciferase Immunoprecipitation Systems (LIPS) in patients from three disease cohorts including those with pathogenic anti-interferon-γ autoantibodies (IFN-γ AAB), HIV and Sjögren’s syndrome (SjS) to determine if their antibody profiles differed from control subjects. The IFN-γ AAB patients compared to controls demonstrated statistically higher levels of antibodies against VZV (p=0.0003), EBV (p=0.002), CMV (p=0.003), and C. albicans (p=0.03), but lower antibody levels against poliovirus (p=0.04). Comparison of HIV patients with blood donor controls revealed that the patients had higher levels of antibodies against CMV (p=0.0008), HSV-2 (p=0.0008), EBV (p=0.001), and C. albicans (p=0.01), but showed decreased levels of antibodies against coxsackievirus B4 (p=0.0008), poliovirus (p=0.0005), and HHV-6B (p=0.002). Lastly, SjS patients had higher levels of anti-EBV antibodies (p=0.03), but lower antibody levels against several enteroviruses including a newly identified picornavirus, HCoSV-A (p=0.004), coxsackievirus B4 (p=0.04), and poliovirus (p=0.02). For the IFN-γ AAB and HIV cohorts, principal component analysis revealed unique antibody clusters that showed the potential to discriminate patients from controls. The results suggest that antibody profiles against these and likely other common infectious agents may yield insight into the interplay between exposure to infectious agents, dysbiosis, adaptive immunity and disease activity. 相似文献
926.
927.
Leslie W. Tari Michael Trzoss Daniel C. Bensen Xiaoming Li Zhiyong Chen Thanh Lam Junhu Zhang Christopher J. Creighton Mark L. Cunningham Bryan Kwan Mark Stidham Karen J. Shaw Felice C. Lightstone Sergio E. Wong Toan B. Nguyen Jay Nix John Finn 《Bioorganic & medicinal chemistry letters》2013,23(5):1529-1536
The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity. 相似文献
928.
Thomas V. Magee Seungil Han Sandra P. McCurdy Thuy-Trinh Nguyen Karl Granskog Eric S. Marr Bruce A. Maguire Michael D. Huband Jinshan Michael Chen Timothy A. Subashi Veerabahu Shanmugasundaram 《Bioorganic & medicinal chemistry letters》2013,23(6):1727-1731
A novel series of 3-O-carbamoyl erythromycin A derived analogs, labeled carbamolides, with activity versus resistant bacterial isolates of staphylococci (including macrolide and oxazolidinone resistant strains) and streptococci are reported. An (R)-2-aryl substituent on a pyrrolidine carbamate appeared to be critical for achieving potency against resistant strains. Crystal structures showed a distinct aromatic interaction between the (R)-2-aryl (3-pyridyl for 4d) substituent on the pyrrolidine and G2484 (G2505, Escherichia coli) of the Deinococcus radiodurans 50S ribosome (3.2 Å resolution). 相似文献
929.
Gang Hua Qi Zhang Rui Zhang Amir M. Abdullah Paul J. Linser Michael J. Adang 《Insect biochemistry and molecular biology》2013,43(2):153-161
In an effort to study the mode of action of Cry11Ba, we identified toxin binding proteins in Anopheles gambiae larval midgut and investigated their receptor roles. Previously, an aminopeptidase (AgAPN2) and an alkaline phosphatase (AgALP1) were identified as receptors for Cry11Ba toxin in A. gambiae. However, an A. gambiae cadherin (AgCad1) that bound Cry11Ba with low affinity (Kd = 766 nM) did not support a receptor role of AgCad1 for Cry11Ba. Here, we studied a second A. gambiae cadherin (AgCad2) that shares 14% identity to AgCad1. Immunohistochemical study showed that the protein is localized on A. gambiae larval midgut apical membranes. Its cDNA was cloned and the protein was analyzed as a transmembrane protein containing 14 cadherin repeats. An Escherichia coli expressed CR14MPED fragment of AgCad2 bound Cry11Ba with high affinity (Kd = 11.8 nM), blocked Cry11Ba binding to A. gambiae brush border vesicles and reduced Cry11Ba toxicity in bioassays. Its binding to Cry11Ba could be completely competed off by AgCad1, but only partially competed by AgALP1. The results are evidence that AgCad2 may function as a receptor for Cry11Ba in A. gambiae larvae. 相似文献
930.
Brigitte Marazzi Elena Conti Michael J. Sanderson Michelle M. McMahon Judith L. Bronstein 《Annals of botany》2013,111(6):1263-1275