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951.
Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus 总被引:62,自引:0,他引:62
Horikawa Y Oda N Cox NJ Li X Orho-Melander M Hara M Hinokio Y Lindner TH Mashima H Schwarz PE del Bosque-Plata L Horikawa Y Oda Y Yoshiuchi I Colilla S Polonsky KS Wei S Concannon P Iwasaki N Schulze J Baier LJ Bogardus C Groop L Boerwinkle E Hanis CL Bell GI 《Nature genetics》2000,26(2):163-175
Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes. 相似文献
952.
I. Johnsen 《Cellular and molecular life sciences : CMLS》1986,42(5):503-507
Conclusion The biological indication approach is necessary in environmental management, and should go hand in hand with conventional analytical-chemical techniques. It is essential that the characterization of environmental quality should also include the observations of skilled biologists. If not, we are likely in the future to face many unforeseen environmental problems at a very late stage of their development. The use of biological indicators represents one aspect of the biologist's characterization of environmental quality. 相似文献
953.
Vrontou S Petrou P Meyer BI Galanopoulos VK Imai K Yanagi M Chowdhury K Scambler PJ Chalepakis G 《Nature genetics》2003,34(2):209-214
Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Postnatally, homozygous Fras1 mutants have fusion of the eyelids and digits and unilateral renal agenesis or dysplasia. The defects observed in Fras1-/- mice phenocopy those of the existing bl (blebbed) mouse mutants, which have been considered a model for the human genetic disorder Fraser syndrome. We show that bl/bl homozygous embryos are devoid of Fras1 protein, consistent with the finding that Fras1 is mutated in these mice. In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human. 相似文献
954.
Magnetic and flotation studies of banded hematite quartzite (BHQ) ore for the production of pellet grade concentrate 下载免费PDF全文
To identify and establish beneficiation techniques for banded hematite quartzite (BHQ) iron ore, a comprehensive research on BHQ ore treatment was carried out. The BHQ ore was assayed as 38.9wt% Fe, 42.5wt% SiO2, and 1.0wt% Al2O3. In this ore, hematite and quartz are present as the major mineral phases where goethite, martite, and magnetite are present in small amounts. The liberation of hematite particles can be enhanced to about 82% by reducing the particle size to below 63 μm. The rejection of silica particles can be obtained by magnetic and flotation separation techniques. Overall, the BHQ ore can be enriched to 65.3wt% Fe at 61.9% iron recovery. A flowsheet has been suggested for the commercial exploitation of the BHQ ore. 相似文献
955.
956.
Pang SS Berry R Chen Z Kjer-Nielsen L Perugini MA King GF Wang C Chew SH La Gruta NL Williams NK Beddoe T Tiganis T Cowieson NP Godfrey DI Purcell AW Wilce MC McCluskey J Rossjohn J 《Nature》2010,467(7317):844-848
The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR β-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent αβ T-cell lineage differentiation. Whereas αβTCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling, pre-TCR-induced signalling occurs by means of a ligand-independent dimerization event. The pre-TCR comprises an invariant α-chain (pre-Tα) that pairs with any TCR β-chain (TCRβ) following successful TCR β-gene rearrangement. Here we provide the basis of pre-Tα-TCRβ assembly and pre-TCR dimerization. The pre-Tα chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR α-chain; nevertheless, the mode of association between pre-Tα and TCRβ mirrored that mediated by the Cα-Cβ domains of the αβTCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-Tα domain to interact with the variable (V) β domain through residues that are highly conserved across the Vβ and joining (J) β gene families, thus mimicking the interactions at the core of the αβTCR's Vα-Vβ interface. Disruption of this pre-Tα-Vβ dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-Tα chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR β-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-Tα represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex. 相似文献
957.
Alafara A. Baba Kuranga I. Ayinla Folahan A. Adekola Rafiu B. Bale Malay K. Ghosh Abdul G. F. Alabi Abdul R. Sheik Ismael O. Folorunso 《矿物冶金与材料学报》2013,20(11):1021-1028
The dissolution kinetics of a Nigerian chalcopyrite ore in hydrochloric acid was studied in this article. Acid concentration, reaction temperature, and ore particle size were chosen as experimental parameters. The chemical and morphological studies of the ore before and after leaching at optimal conditions were carried out by X-ray diffraction (XRD) and scanning electron microscopy (SEM). It is revealed that increasing the acid concentration and system temperature and decreasing the ore particle size greatly enhances the dissolution rate. The dissolution kinetics was found to follow the shrinking core model for the diffusion control mechanism where the activation energy (Ea) of 32.92 kJ·mol?1 was obtained for the process and supported by morphological changes at a higher dissolution of 91.33%. 相似文献
958.
Short Report: Cyclic patterns of incidence rate for skin malignant melanoma: association with heliogeophysical activity 下载免费PDF全文
Background: Our previous studies revealed cyclicity in the incidence rate of skin malignant melanoma (SMM; ICD9, Dx: 172) in the Czech Republic (period T=7.50~7.63 years), UK (T= 11.00 years) and Bulgaria (T= 12.20 years). Incidences com- pared with the sunspot index Rz (lag-period dT=+2, +4, +6, + 10 or + 12 years) have indicated that maximal rates are most likely to appear on descending slopes of the ;ll-year solar cycle, i.e., out of phase. We summarized and explored more deeply these cyclic variations and discussed their possible associations with heliogeophysical activity (HGA) components exhibiting similar cyclicity. Methods: Annual incidences of SMM from 5 countries (Czech Republic, UK, Bulgaria, USA and Canada) over various time spans during the years 1964-1992 were analyzed and their correlations with cyclic Rz (sunspot number) and aa (planetary geomagnetic activity) indices were summarized. Periodogram regression analysis with trigonometric approximation and phase-correlation analysis were applied. Results: Previous findings on SMM for the Czech Republic, UK and Bulgaria have been validated, and cyclic patterns have been revealed for USA (T=8.63 years, P〈0.05) and Canada (Ontario, T=9.91 years, P〈0.10). Also, various 'hypercycles' were established (T=45.5, 42.0, 48.25, 34.5 and 26.5 years, respectively) describing long-term cyclic incidence patterns. The association of SMM for USA and Canada with Rz (dT=+6 and +7 years, respectively) and aa (dT=-10 and +9 years, respectively) was described. Possible interactions of cyclic non-photic influences (UV irradiation, Schumann resonance signal, low-frequency geomagnetic fluctuations) with brain waves absorbance, neuronal calcium dynamics, neuro-endocrine axis modulation, melatonin/serotonin disbalance and skin neuro-immunity impairment as likely causal pathways in melanoma appearance, were also discussed. Conclusion: The above findings on cyclicity and temporal assoc 相似文献
959.
Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal. 相似文献
960.
Greenberg JI Shields DJ Barillas SG Acevedo LM Murphy E Huang J Scheppke L Stockmann C Johnson RS Angle N Cheresh DA 《Nature》2008,456(7223):809-813
Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) through their cognate receptors on endothelial cells and vascular smooth muscle cells (VSMCs), respectively. PDGF induces neovascularization by priming VSMCs/pericytes to release pro-angiogenic mediators. Although VEGF directly stimulates endothelial cell proliferation and migration, its role in pericyte biology is less clear. Here we define a role for VEGF as an inhibitor of neovascularization on the basis of its capacity to disrupt VSMC function. Specifically, under conditions of PDGF-mediated angiogenesis, VEGF ablates pericyte coverage of nascent vascular sprouts, leading to vessel destabilization. At the molecular level, VEGF-mediated activation of VEGF-R2 suppresses PDGF-Rbeta signalling in VSMCs through the assembly of a previously undescribed receptor complex consisting of PDGF-Rbeta and VEGF-R2. Inhibition of VEGF-R2 not only prevents assembly of this receptor complex but also restores angiogenesis in tissues exposed to both VEGF and PDGF. Finally, genetic deletion of tumour cell VEGF disrupts PDGF-Rbeta/VEGF-R2 complex formation and increases tumour vessel maturation. These findings underscore the importance of VSMCs/pericytes in neovascularization and reveal a dichotomous role for VEGF and VEGF-R2 signalling as both a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation. 相似文献