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921.
922.
Rajagopalan H Jallepalli PV Rago C Velculescu VE Kinzler KW Vogelstein B Lengauer C 《Nature》2004,428(6978):77-81
Aneuploidy, an abnormal chromosome number, has been recognized as a hallmark of human cancer for nearly a century; however, the mechanisms responsible for this abnormality have remained elusive. Here we report the identification of mutations in hCDC4 (also known as Fbw7 or Archipelago) in both human colorectal cancers and their precursor lesions. We show that genetic inactivation of hCDC4, by means of targeted disruption of the gene in karyotypically stable colorectal cancer cells, results in a striking phenotype associated with micronuclei and chromosomal instability. This phenotype can be traced to a defect in the execution of metaphase and subsequent transmission of chromosomes, and is dependent on cyclin E--a protein that is regulated by hCDC4 (refs 2-4). Our data suggest that chromosomal instability is caused by specific genetic alterations in a large fraction of human cancers and can occur before malignant conversion. 相似文献
923.
Earl PL Americo JL Wyatt LS Eller LA Whitbeck JC Cohen GH Eisenberg RJ Hartmann CJ Jackson DL Kulesh DA Martinez MJ Miller DM Mucker EM Shamblin JD Zwiers SH Huggins JW Jahrling PB Moss B 《Nature》2004,428(6979):182-185
The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA. 相似文献
924.
925.
926.
Abrescia NG Cockburn JJ Grimes JM Sutton GC Diprose JM Butcher SJ Fuller SD San Martín C Burnett RM Stuart DI Bamford DH Bamford JK 《Nature》2004,432(7013):68-74
The structure of the membrane-containing bacteriophage PRD1 has been determined by X-ray crystallography at about 4 A resolution. Here we describe the structure and location of proteins P3, P16, P30 and P31. Different structural proteins seem to have specialist roles in controlling virus assembly. The linearly extended P30 appears to nucleate the formation of the icosahedral facets (composed of trimers of the major capsid protein, P3) and acts as a molecular tape-measure, defining the size of the virus and cementing the facets together. Pentamers of P31 form the vertex base, interlocking with subunits of P3 and interacting with the membrane protein P16. The architectural similarities with adenovirus and one of the largest known virus particles PBCV-1 support the notion that the mechanism of assembly of PRD1 is scaleable and applies across the major viral lineage formed by these viruses. 相似文献
927.
928.
In quantum computation non classical features such as superposition states and entanglement are used to solve problems in new ways, impossible on classical digital computers.We illustrate by Deutsch algorithm how a quantum computer can use superposition states to outperform any classical computer. We comment on the view of a quantum computer as a massive parallel computer and recall Amdahls law for a classical parallel computer. We argue that the view on quantum computation as a massive parallel computation disregards the presence of entanglement in a general quantum computation and the non classical way in which parallel results are combined to obtain the final output. 相似文献
929.
Isolation of human epidermal stem cells by adherence and the reconstruction of skin equivalents 总被引:47,自引:0,他引:47
Kim DS Cho HJ Choi HR Kwon SB Park KC 《Cellular and molecular life sciences : CMLS》2004,61(21):2774-2781
The isolation of human epidermal stem cells is critical for their clinical applications. In the present study, we isolated three populations of epidermal keratinocytes according to their ability to adhere to collagen type IV: i.e., rapidly adhering (RA), slowly adhering (SA), and non-adhering (NA) cells. The aim of this study was to characterize RA cells and to investigate the possibility of using these cells for epidermis reconstruction. To identify RA cells, flow cytometric analysis was performed using anti-6 integrin and anti-CD71 antibodies. RA cells express high levels of 6 integrin and low levels of CD71, which are considered as markers of an epidermal stem cell nature. Furthermore, electron microscopy showed that RA cells are small and have a high nuclear to cytoplasmic ratio, whereas SA and NA cells have well-developed cellular organelles and abundant tonofilaments. Western blot analysis showed that RA cells are slow cycling and express p63, a putative epidermal stem cell marker, whereas SA and NA cells express c-Myc, which is known to regulate stem cell fate. To compare epidermal regenerative abilities, skin equivalents (SEs) were made using RA, SA, and NA cells. The epidermis constructed from RA cells was well formed compared to those formed from SA or NA cells. In addition, only SEs with RA cells expressed 6 integrin and 1 integrin at the basal layer. These results indicate that RA cells represent epidermal stem cells and are predominately comprised of stem cells. Therefore, the isolation of RA cells using a simple technique offers a potential route to their clinical application, because they are easily isolated and provide a high yield of epidermal stem cells.Received 2 July 2004; received after revision 20 August 2004; accepted 10 September 2004 相似文献
930.
Bendahan D Giannesini B Cozzone PJ 《Cellular and molecular life sciences : CMLS》2004,61(9):1001-1015
Muscle fatigue, which is defined as the decline in muscle performance during exercise, may occur at different sites along the pathway from the central nervous system through to the intramuscular contractile machinery. Historically, both impairment of neuromuscular transmission and peripheral alterations within the muscle have been proposed as causative factors of fatigue development. However, according to more recent studies, muscle energetics play a key role in this process. Intramyoplasmic accumulation of inorganic phosphate (Pi) and limitation in ATP availability have been frequently evoked as the main mechanisms leading to fatigue. Although attractive, these hypotheses have been elaborated on the basis of experimental results obtained in vitro, and their physiological relevance has never been clearly demonstrated in vivo. In that context, noninvasive methods such as 31-phosphorus magnetic resonance spectroscopy and surface electromyography have been employed to understand both metabolic and electrical aspects of muscle fatigue under physiological conditions. Mapping of muscles activated during exercise is another interesting issue which can be addressed using magnetic resonance imaging (MRI). Exercise-induced T2 changes have been used in order to locate activated muscles and also as a quantitative index of exercise intensity. The main results related to both issues, i.e. the metabolic and electrical aspects of fatigue and the MRI functional investigation of exercising muscle, are discussed in the present review.Received 4 September 2003; received after revision 4 December 2003; accepted 22 December 2003 相似文献