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991.
In the accompanying paper, we found, using molecular dynamics calculations, four domains of the ras-specific SOS guanine nucleotide exchange protein (residues 589-601, 654-675, 746-761, and 980-989) that differ markedly in conformation when SOS is complexed with either oncogenic (Val 12-) ras-p21 or wild-type ras-p21. Three of these domains contain three crystallographically undefined loops that we modeled in these calculations, and one is a newly identified non-loop domain containing SOS residues 980-989. We have now synthesized peptides corresponding to these four domains and find that all of them block Val 12-ras-p21-induced oocyte maturation. All of them also block insulin-induced oocyte maturation, but two of these peptides, corresponding to SOS residues 589-601 and 980-989, block oncogenic ras to a significantly greater extent. These results suggest that SOS contains domains, including the three loop domains, that are important for ras signaling and that several of these domains can activate different pathways specific to oncogenic or wild-type ras-p21. 相似文献
992.
A nodule-specific dicarboxylate transporter from alder is a member of the peptide transporter family 下载免费PDF全文
Jeong J Suh S Guan C Tsay YF Moran N Oh CJ An CS Demchenko KN Pawlowski K Lee Y 《Plant physiology》2004,134(3):969-978
Alder (Alnus glutinosa) and more than 200 angiosperms that encompass 24 genera are collectively called actinorhizal plants. These plants form a symbiotic relationship with the nitrogen-fixing actinomycete Frankia strain HFPArI3. The plants provide the bacteria with carbon sources in exchange for fixed nitrogen, but this metabolite exchange in actinorhizal nodules has not been well defined. We isolated an alder cDNA from a nodule cDNA library by differential screening with nodule versus root cDNA and found that it encoded a transporter of the PTR (peptide transporter) family, AgDCAT1. AgDCAT1 mRNA was detected only in the nodules and not in other plant organs. Immunolocalization analysis showed that AgDCAT1 protein is localized at the symbiotic interface. The AgDCAT1 substrate was determined by its heterologous expression in two systems. Xenopus laevis oocytes injected with AgDCAT1 cRNA showed an outward current when perfused with malate or succinate, and AgDCAT1 was able to complement a dicarboxylate uptake-deficient Escherichia coli mutant. Using the E. coli system, AgDCAT1 was shown to be a dicarboxylate transporter with a K(m) of 70 microm for malate. It also transported succinate, fumarate, and oxaloacetate. To our knowledge, AgDCAT1 is the first dicarboxylate transporter to be isolated from the nodules of symbiotic plants, and we suggest that it may supply the intracellular bacteria with dicarboxylates as carbon sources. 相似文献
993.
Huang D Poon SF Chapman DF Chung J Cramer M Reger TS Roppe JR Tehrani L Cosford ND Smith ND 《Bioorganic & medicinal chemistry letters》2004,14(22):5473-5476
Structure-activity relationship studies on 3-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitrile 2 led to the discovery of 2-(2-[3-(pyridin-3-yloxy)phenyl]-2H-tetrazol-5-yl)pyridine (10)-a highly potent and selective mGlu5 receptor antagonist with good brain penetration and in vivo receptor occupancy in rat and cross-species oral bioavailability. 相似文献
994.
Glucose ingestion attenuates the exercise-induced increase in circulating heat shock protein 72 and heat shock protein 60 in humans 下载免费PDF全文
Febbraio MA Mesa JL Chung J Steensberg A Keller C Nielsen HB Krustrup P Ott P Secher NH Pedersen BK 《Cell stress & chaperones》2004,9(4):390-396
Heat shock protein (Hsp) 72 is a cytosolic stress protein that is highly inducible by several factors including exercise. Hsp60 is primarily mitochondrial in cellular location, plays a key role in the intracellular protein translocation and cytoprotection, is increased in skeletal muscle by exercise, and is found in the peripheral circulation of healthy humans. Glucose deprivation increases Hsp72 in cultured cells, whereas reduced glycogen availability elevates Hsp72 in contracting human skeletal muscle. To determine whether maintained blood glucose during exercise attenuates the exercise-induced increase in intramuscular and circulating Hsp72 and Hsp60, 6 males performed 120 minutes of semirecumbent cycling at approximately 65% maximal oxygen uptake on 2 occasions while ingesting either a 6.4% glucose (GLU) or sweet placebo (CON) beverage throughout exercise. Muscle biopsies, obtained before and immediately after exercise, were analyzed for Hsp72 and Hsp60 protein expression. Blood samples were simultaneously obtained from a brachial artery, a femoral vein, and the hepatic vein before and during exercise for the analysis of serum Hsp72 and Hsp60. Leg and hepatosplanchnic blood flow were measured to determine Hsp72-Hsp60 flux across these tissue beds. Neither exercise nor glucose ingestion affected the Hsp72 or Hsp60 protein expression in, or their release from, contracting skeletal muscle. Arterial serum Hsp72 increased (P < 0.05) throughout exercise in both trials but was attenuated (P < 0.05) in GLU. This may have been in part because of the increased (P < 0.05) hepatosplanchnic Hsp72 release in CON, being totally abolished (P < 0.05) in GLU. Serum Hsp60 increased (P < 0.05) after 60 minutes of exercise in CON before returning to resting levels at 120 minutes. In contrast, no exercise-induced increase in serum Hsp60 was observed in GLU. We detected neither hepatosplanchnic nor contracting limb Hsp60 release in either trial. In conclusion, maintaining glucose availability during exercise attenuates the circulating Hsp response in healthy humans. 相似文献
995.
Kim DW Lee JH Park SK Yang WM Jeon GS Lee YH Chung CK Cho SS 《Neurochemical research》2007,32(9):1460-1468
Glycogen synthase kinase 3β (GSK3β) is believed to play important roles in the regulation of synaptic plasticity, cell survival
and circadian rhythms in the mature CNS. However, although several studies have been focused on the GSK3β, little is known
about GSK3β changes in glial cells under neuropathological conditions. In this study, we evaluated the expressions of molecules
associated with the GSK3β signaling pathway, following the induction of an excitotoxic lesion in mouse brain by kainic acid
(KA) injection, which caused pyramidal cell degeneration in the hippocampal CA3 region. In injured hippocampi, Ser47-Akt (protein
kinase B, PKB) phosphorylation increased from 4 h until 1 day post-injection (PI). Ser9-GSK3β and Ser133-cAMP responsive element-binding
protein (CREB) phosphorylations showed similar spatiotemporal patterns in hippocampi at 1 day until 3 days PI. Double immunohistochemistry
also showed that these phosphorylated forms of Akt, GSK3β and CREB were expressed in astrocytes. For the first time, our data
demonstrate the injury-induced astrocytic changes in the levels of phosphorylation of Akt, -GSK3β and -CREB in vivo, which
may reflect mechanisms of glial cells protection or adaptive response to damage.
DW Kim and JH Lee contributed equally to this work. 相似文献
996.
Flores A Nisola GM Cho E Gwon EM Kim H Lee C Park S Chung WJ 《Bioprocess and biosystems engineering》2007,30(3):197-205
The performance of enriched sludge augmented with the B21 strain of Alcaligenes defragrans was compared with that of enriched sludge, as well as with pure Alcaligenes defragrans B21, in the context of a sulfur-oxidizing denitrification (SOD) process. In synthetic wastewater treatment containing 100–1,000 mg
NO3−-N/L, the single strain-seeded system exhibited superior performance, featuring higher efficiency and a shorter startup period,
provided nitrate loading rate was less than 0.2 kg NO3−-N/m3 per day. At nitrate loading rate of more than 0.5 kg NO3−-N/m3 per day, the bioaugmented sludge system showed higher resistance to shock loading than two other systems. However, no advantage
of the bioaugmented system over the enriched sludge system without B21 strain was observed in overall efficiency of denitrification.
Both the bioaugmented sludge and enriched sludge systems obtained stable denitrification performance of more than 80% at nitrate
loading rate of up to 2 kg NO3−-N/m3 per day. 相似文献
997.
A fluorescent method was developed for the detection of unpaired and mismatched DNAs using a MutS-fluorophore conjugate. The fluorophore, 2-(4'-(iodoacetoamido)anilino) naphthalene-6-sulfonic acid (IAANS), was site-specifically attached to the 469 position of Thermus aquaticus (Taq.) MutS mutant (C42A/T469C). The fluorophore labeled residue located at the dimer interface of the protein undergoes a drastic conformational change upon binding with mismatched DNA. The close proximity of the two identical fluorescent molecules presumably causes the self-quenching of the fluorophore, since fluorescence emission of the biosensor decreases with increasing concentrations of mismatched DNA. The order of binding affinity for each unpaired and mismatched DNA obtained by this method was DeltaT (Kd=52 nM)>GT (62 nM)>DeltaC (130 nM)>CT (160 nM)>DeltaG (170 nM)>DeltaA (250 nM)>CC (720 nM)>AT (950 nM). This order is comparable to the previous results of the gel mobility shift assay. Thus, this method can be a simple, useful tool for elucidating the mechanism of DNA mismatch repair as well as a novel probe for detecting of genetic mutation. 相似文献
998.
R-type pyocin is a bacteriophage tail-shaped bacteriocin produced by Pseudomonas aeruginosa, but its physiological roles are relatively unknown. Here we describe a role of R-type pyocin in the competitive growth advantages between P. aeruginosa strains. Partial purification and gene disruption revealed that the major killing activity from the culture supernatant of PA14 is attributed to R-type pyocin, neither F-type nor S-type pyocins. These findings may provide insight into the forces governing P. aeruginosa population dynamics to promote and maintain its biodiversity. 相似文献
999.
MOTIVATION: The identification and characterization of susceptibility genes that influence the risk of common and complex diseases remains a statistical and computational challenge in genetic association studies. This is partly because the effect of any single genetic variant for a common and complex disease may be dependent on other genetic variants (gene-gene interaction) and environmental factors (gene-environment interaction). To address this problem, the multifactor dimensionality reduction (MDR) method has been proposed by Ritchie et al. to detect gene-gene interactions or gene-environment interactions. The MDR method identifies polymorphism combinations associated with the common and complex multifactorial diseases by collapsing high-dimensional genetic factors into a single dimension. That is, the MDR method classifies the combination of multilocus genotypes into high-risk and low-risk groups based on a comparison of the ratios of the numbers of cases and controls. When a high-order interaction model is considered with multi-dimensional factors, however, there may be many sparse or empty cells in the contingency tables. The MDR method cannot classify an empty cell as high risk or low risk and leaves it as undetermined. RESULTS: In this article, we propose the log-linear model-based multifactor dimensionality reduction (LM MDR) method to improve the MDR in classifying sparse or empty cells. The LM MDR method estimates frequencies for empty cells from a parsimonious log-linear model so that they can be assigned to high-and low-risk groups. In addition, LM MDR includes MDR as a special case when the saturated log-linear model is fitted. Simulation studies show that the LM MDR method has greater power and smaller error rates than the MDR method. The LM MDR method is also compared with the MDR method using as an example sporadic Alzheimer's disease. 相似文献
1000.
Nobuo Imai Hiromitsu Samejima Andreas Langner Robert C. Ong Satoshi Kita Jupiri Titin Arthur Y. C. Chung Peter Lagan Ying Fah Lee Kanehiro Kitayama 《PloS one》2009,4(12)