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101.
Snake envenomation is a socio-medical problem of considerable magnitude. About 2.5 million people are bitten by snakes annually,
more than 100,000 fatally. However, although bites can be deadly, snake venom is a natural biological resource that contains
several components of potential therapeutic value. Venom has been used in the treatment of a variety of pathophysiological
conditions in Ayurveda, homeopathy and folk medicine. With the advent of biotechnology, the efficacy of such treatments has
been substantiated by purifying components of venom and delineating their therapeutic properties. This review will focus on
certain snake venom components and their applications in health and disease.
Received 6 July 2006; received after revision 14 August 2006; accepted 28 September 2006 相似文献
102.
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance 总被引:3,自引:0,他引:3
Balaraman Y Limaye AR Levey AI Srinivasan S 《Cellular and molecular life sciences : CMLS》2006,63(11):1226-1235
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading
cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the
serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in
the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review,
we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor
protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt,
Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.
Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006 相似文献
103.
Foser S Redwanz I Ebeling M Heizmann CW Certa U 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2387-2396
A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. We show here that costimulation with IFN-alpha and transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. A DNA microarray-based search for proliferation control genes involved that are cooperatively activated by IFN-alpha and TGF-beta, yielded 28 genes. Among these are the insulin-like growth factor-binding protein 3 (IGFBP3) and the calcium-binding protein S100A2; we demonstrate, that recombinant IGFBP3 protein is a potent growth inhibitor requiring TGF-beta activity. The antiproliferative activity of S100A2 is significantly enhanced by IFN-alpha in stably transfected ME15 or D10 cell lines. We show for the first time that IFN-alpha is a potent inducer of intracellular calcium release required for activation of S100A2. Our study provides a functional link between IFN-alpha and TGF-beta signaling and extends the function of IFN signaling to calcium-sensitive processes. 相似文献
104.
Niimura N Arai S Kurihara K Chatake T Tanaka I Bau R 《Cellular and molecular life sciences : CMLS》2006,63(3):285-300
Neutron diffraction provides an experimental method of directly locating hydrogen atoms in proteins, a technique complimentary to ultra-high-resolution [1, 2] X-ray diffraction. Three different types of neutron diffractometers for biological macromolecules have been constructed in Japan, France and the United States, and they have been used to determine the crystal structures of proteins up to resolution limits of 1.5-2.5 A. Results relating to hydrogen positions and hydration patterns in proteins have been obtained from these studies. Examples include the geometrical details of hydrogen bonds, H/D exchange in proteins and oligonucleotides, the role of hydrogen atoms in enzymatic activity and thermostability, and the dynamical behavior of hydration structures, all of which have been extracted from these structural results and reviewed. Other techniques, such as the growth of large single crystals, the preparation of fully deuterated proteins, the use of cryogenic techniques, and a data base of hydrogen and hydration in proteins, will be described. 相似文献
105.
Shin JM Vagin O Munson K Kidd M Modlin IM Sachs G 《Cellular and molecular life sciences : CMLS》2008,65(2):264-281
Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration;
therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor
were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell
hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are
the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities.
Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of
a novel class of agents, the acid pump antagonists.
Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007 相似文献
106.
Dolezel D Zdechovanova L Sauman I Hodkova M 《Cellular and molecular life sciences : CMLS》2008,65(6):964-969
Current models state that insect peripheral oscillators are directly responsive to light, while mammalian peripheral clock
genes are coordinated by a master clock in the brain via intermediate factors, possibly hormonal. We show that the expression
levels of two circadian clock genes, period (per) and Par Domain Protein 1 (Pdp1) in the peripheral tissue of an insect model species, the linden bug Pyrrhocoris apterus, are inversely affected by contrasting photoperiods. The effect of photoperiod on per and Pdp1 mRNA levels was found to be mediated by the corpus allatum, an endocrine gland producing juvenile hormone. Our results
provide the first experimental evidence for the effect of an endocrine gland on circadian clock gene expression in insects.
Received 31 October 2007; received after revision 7 January 2008; accepted 9 January 2008
D. Dolezel, L. Zdechovanova: These authors contributed equally to this work. 相似文献
107.
108.
Kao WH Klag MJ Meoni LA Reich D Berthier-Schaad Y Li M Coresh J Patterson N Tandon A Powe NR Fink NE Sadler JH Weir MR Abboud HE Adler SG Divers J Iyengar SK Freedman BI Kimmel PL Knowler WC Kohn OF Kramp K Leehey DJ Nicholas SB Pahl MV Schelling JR Sedor JR Thornley-Brown D Winkler CA Smith MW Parekh RS;Family Investigation of Nephropathy Diabetes Research Group 《Nature genetics》2008,40(10):1185-1192
As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. 相似文献
109.
Arachiche A Badirou I Dachary-Prigent J Garcin I Geldwerth-Feniger D Kerbiriou-Nabias D 《Cellular and molecular life sciences : CMLS》2008,65(23):3861-3871
Rapid Ca2+-dependent phospholipid (PL) reorganization (scrambling) at the plasma membrane is a mechanism common to hematopoietic cells
exposing procoagulant phosphatidylserine (PS). The aim of this research was to determine whether activation of the extracellular
signal-regulated kinase (ERK) pathway was required for PL scrambling, based on a single report analyzing both responses induced
by Ca2+ ionophores in megakaryoblastic HEL cells. Ca2+ ionophore-stimulated ERK phosphorylation was induced in platelets without external Ca2+, whereas exogenous Ca2+ entry was crucial for ERK activation in Jurkat T cells. In both cells, membrane scrambling only occurred following Ca2+ entry and was not blocked by inhibiting ERK phosphorylation. Furthermore, ERK proteins are strongly phosphorylated in transformed
B lymphoblastic cell lines, which do not expose PS in their resting state. Overall, the data demonstrated that ERK activation
and membrane scrambling are independent mechanisms.
A. Arachiche, I. Badirou: These authors contributed equally to this work.
Received 18 June 2008; received after revision 24 September 2008; accepted 1 October 2008 相似文献
110.
Loos RJ Lindgren CM Li S Wheeler E Zhao JH Prokopenko I Inouye M Freathy RM Attwood AP Beckmann JS Berndt SI;Prostate Lung Colorectal Ovarian 《Nature genetics》2008,40(6):768-775
To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits. 相似文献