全文获取类型
收费全文 | 13201篇 |
免费 | 918篇 |
国内免费 | 4篇 |
专业分类
14123篇 |
出版年
2023年 | 75篇 |
2022年 | 119篇 |
2021年 | 214篇 |
2020年 | 129篇 |
2019年 | 185篇 |
2018年 | 326篇 |
2017年 | 305篇 |
2016年 | 427篇 |
2015年 | 655篇 |
2014年 | 661篇 |
2013年 | 886篇 |
2012年 | 1040篇 |
2011年 | 1043篇 |
2010年 | 707篇 |
2009年 | 553篇 |
2008年 | 729篇 |
2007年 | 729篇 |
2006年 | 747篇 |
2005年 | 635篇 |
2004年 | 625篇 |
2003年 | 576篇 |
2002年 | 540篇 |
2001年 | 269篇 |
2000年 | 212篇 |
1999年 | 202篇 |
1998年 | 127篇 |
1997年 | 119篇 |
1996年 | 96篇 |
1995年 | 57篇 |
1994年 | 73篇 |
1993年 | 52篇 |
1992年 | 85篇 |
1991年 | 72篇 |
1990年 | 65篇 |
1989年 | 55篇 |
1988年 | 59篇 |
1987年 | 58篇 |
1986年 | 48篇 |
1985年 | 53篇 |
1984年 | 66篇 |
1983年 | 42篇 |
1982年 | 47篇 |
1981年 | 39篇 |
1980年 | 34篇 |
1979年 | 33篇 |
1978年 | 24篇 |
1977年 | 24篇 |
1976年 | 18篇 |
1974年 | 23篇 |
1973年 | 30篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
João Ricardo Sato Claudinei Eduardo Biazoli Ana Paula Arantes Bueno Arthur Caye Pedro Mario Pan Marcos Santoro Jessica Honorato-Mauer Giovanni Abrahão Salum Marcelo Queiroz Hoexter Rodrigo Affonseca Bressan Andrea Parolin Jackowski Euripedes Constantino Miguel Sintia Belangero Luis Augusto Rohde 《Genes, Brain & Behavior》2023,22(2):e12838
102.
Roger S. McIntyre Mohammad Alsuwaidan Bernhard T. Baune Michael Berk Koen Demyttenaere Joseph F. Goldberg Philip Gorwood Roger Ho Siegfried Kasper Sidney H. Kennedy Josefina Ly-Uson Rodrigo B. Mansur R. Hamish McAllister-Williams James W. Murrough Charles B. Nemeroff Andrew A. Nierenberg Joshua D. Rosenblat Gerard Sanacora Alan F. Schatzberg Richard Shelton Stephen M. Stahl Madhukar H. Trivedi Eduard Vieta Maj Vinberg Nolan Williams Allan H. Young Mario Maj 《World psychiatry》2023,22(3):394-412
Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population. 相似文献
103.
M. Berrocal S. Huerta J. Rodríguez M. Pérez-Leblic M. E. Arias 《World journal of microbiology & biotechnology》1996,12(1):101-102
In surface cultures of Streptomyces cyaneus var. viridochromogenes, NaCl depressed water activity (a
w) without supporting growth. Reducing a
w from 0.987 to 0.951 led to 3- and 4-fold increases in intracellular and extracellular phenol oxidase activities, respectively. 相似文献
104.
Alfonso Pompella Caterina Cambiaggi Silvia Dominici Aldo Paolicchi Roberto Tongiani Mario Comporti 《Histochemistry and cell biology》1996,105(3):173-178
Confocal laser scanning fluorescence microscopy coupled to image analysis was employed in order to develop and evaluate procedures for the appraisal at the single-cell level of: (1) protein-bound 4-hydroxynonenal, the specific product of membrane peroxidation (by means of immunocytochemistry with biotin-avidin revelation); (2) protein oxidation (by reaction of protein carbonyls with 2,4-dinitrophenyl-hydrazine followed by immunocytochemistry of dinitrophenyl moieties); and (3) cellular protein thiols (by direct alkylation of sulfhydryl groups with thiol-specific fluorescent reagents possessing different cell permeabilities). The procedures proved able to reveal the subcellular distribution of cytochemical parameters useful as indices of oxidative stress conditions, and may allow redox phenotyping of isolated cells, which would provide an efficient tool in selected experimental models. 相似文献
105.
Alfonso Pompella Aldo Paolicchi Silvia Dominici Mario Comporti Roberto Tongiani 《Histochemistry and cell biology》1996,106(3):275-282
A number of studies indicate that cell proliferation can be modulated by changes in the redox balance of (soluble and protein)
cellular thiols. Free radical processes, including lipid peroxidation (LPO), can affect such a balance, and a role for LPO
in multistage carcinogenesis has been envisaged. The present study was aimed to assess the relationships between the protein
thiol redox status and the LPO process in chemically induced preneoplastic tissue. The Solt-Farber's initiation-promotion
model of chemical carcinogenesis in the rat liver was used. In fresh cryostat sections, preneoplastic lesions were identified
by the reexpression of γ-glutamyltranspeptidase (GGT) activity. In serial sections, different classes of protein thiols were
stained; in additional sections, LPO was elicited by various prooxidant mixtures and determined thereafter by the hydroxynaphthoic
hydrazide-Fast Blue B procedure. The incubation of sections in the presence of chelated iron plus substrates for GGT activity
leads to the development of LPO in selected section areas closely corresponding to GGT-positive lesions, indicating the ability
of GGT activity to initiate LPO. Protein-reactive thiols, as well as total protein sulfur, were decreased by 20–25% in cells
belonging to GGT-positive preneoplastic nodules, suggesting the occurrence of oxidative conditions in vivo. The incubation
of additional adjacent sections with the prooxidant mixture H2O2 plus iron(II), in order to induce the complete oxidation of lipid present in the section, showed a decreased basal concentration
of oxidizable lipid substrate in GGT-rich areas. The decreased levels of both protein thiols and lipid-oxidizable substrate
in GGT-positive nodules suggest that the observed GGT-dependent path-way of LPO initiation can be chronically operative in
vivo during early stages of chemical carcinogenesis, in cells expressing GGT as part of their transformed phenotype. 相似文献
106.
It has been previously reported that the three-dimensional structures of the NAD-binding and catalytic site of bacterial toxins with ADP-ribosylating activity are superimposable, and that the key amino acids for the enzymatic activity are conserved. The model includes an NAD-binding and catalytic site formed by an α-helix bent over a β-strand, surrounded by two β-strands bearing a Glu and a His, or Arg, that are required for catalysis. We show here that the model can be extended to comprise all proteins with ADP-ribosylating activity known to date, including all eukaryotic mono- and poly-ADP-ribosyltransferases, the bacterial ADP-ribosylating enzymes which do not have toxic activity, and the analogous enzymes encoded by T-even bacteriophages. We show that, in addition to the common Glu and Arg/His amino acids previously identified, the conserved motifs can be extended as follows: (i) the Arg/His motif is usually arom-His/Arg (where 'arom' is an aromatic residue); (ii) in the sequences of the CT group the β-strand forming part of the 'scaffold' of the catalytic cavity has an arom-ph-Ser-Thr-Ser-ph consensus (where 'ph' represents a hydrophobic residue); and (iii) the motif centred in the key glutamic residue is Glu/Gln-X-Glu; while (iv) in the sequences of the DT group the NAD-binding motif is Tyr-X10 -Tyr. We believe that the model proposed not only accounts for all ADP-ribosylating proteins known to date, but it is likely to fit other enzymes (currently being analysed) which possess such an activity. 相似文献
107.
J. C. Rodríguez-Aguilera F. Navarro A. Arroyo F. J. Alcaín J. M. Villalba P. Navas 《Protoplasma》1995,184(1-4):229-232
Summary Ascorbate is stabilized in the presence of HL-60 cells. Our results showed that cAMP derivatives and agents that increase cAMP stimulate the ability of HL-60 cells to stabilize ascorbate. On the other hand, tunicamycin, a glycosilation-interfering agent, inhibited this ability. The ascorbate stabilization in the presence of HL-60 cells has been questioned as a simple chemical effect. Further properties and controls about the enzymatic nature of this stabilization are described and discussed. This data, together with hormonal regulation, support the hypothesis that an enzymatic redox system located at the plasma membrane is responsible of the extracellular ascorbate stabilization by HL-60 cells.Abbreviations AFR
ascorbate free radicals
- FCS
fetal calf serum
- Sp-cAMPS
Sp-cyclic adenosine monophosphothionate
- Rp-cAMPS
Rp-cyclic adenosine monophosphothionate 相似文献
108.
Detlef Michel Hans Hartings Simona Lanzini Manuela Michel Mario Motto Giorgia Romina Riboldi Francesco Salamini Hans-Peter Döring 《Molecular & general genetics : MGG》1995,248(3):287-292
Eight independently isolated unstable alleles of theOpaque2 (O2) locus were analysed genetically and at the DNA level. The whole series of mutations was isolated from a maize strain carrying a wild-typeO2 allele and the transposable elementActivator (Ac) at thewx-m7 allele. Previous work with another unstable allele of the same series has shown that it was indeed caused by the insertion of anAc element. Unexpectedly, the remaining eight mutations were not caused by the designatedAc element, but by other insertions that are structurally similar or identical to one of two different autonomous transposable elements. Six mutations were caused by the insertion of a transposable element of theEnhancer/Suppressor-Mutator (En/Spm) family. Two mutations were the result of the insertion of a transposable element of theBergamo (Bg) family. Genetic tests carried out with plants carrying the unstable mutations demonstrated that all were caused by the insertion of an autonomous transposable element. 相似文献
109.
María-Carmen Rodríguez-Yoldi José-Emilio Mesonero Maríaa-Jesús Rodríguez-Yoldi 《Biological trace element research》1995,50(1):1-11
Zinc is an essential trace element necessary to life. This metal may exert some of its physiological effects by acting directly
on cellular membranes, either by altering permeability or by modulating the activity of membrane-bound enzymes. On the other
hand, calcium is an essential element in a wide variety of cellular activities. The aim of the present work was to study a
possible interaction between zinc and calcium on intestinal transport ofd-galactose in jejunum of rabbit in vitro. In media with Ca2+, when ZnCl2 was present at 0.5 or 1 mM, zinc was found to reduce thed-galactose absorption significantly. In Ca2+-free media, where CaCl2 was omitted and replaced isotonically with choline chloride, the sugar transport was not modified by zinc. Verapamil at 10−6
M (blocking mainly Ca2+ transport) did not modify the inhibitory effect of zinc ond-galactose transport. When 10−6
M of A 23187 (Ca2+-specific ionophore) was added with/without Ca2+ to the media, ZnCl2 produced no change in sugar transport. These results could suggest a possible interaction of calcium and zinc for the same
chemical groups of membrane, which could affect the intestinal absorption of sugars. 相似文献
110.
Marc Pauly Isabelle Kayser Martine Schmitz Fernand Ries François Hentges Mario Dicato 《Journal of molecular evolution》1995,41(6):974-978
The mdr1 gene, first member of the human multidrug-resistance gene family, is a major gene involved in cellular resistance to several drugs used in anticancer chemotherapy. Its product, the drug-excreting P-glycoprotein, shows a bipartite structure formed by two similar adjacent halves. According to one hypothesis, the fusion of two related ancestral genes during evolution could have resulted in this structure. The DNA sequence analysis of the introns located in the region connecting the two halves of the human mdr1 gene revealed a highly conserved poly(CA) · poly (TG) sequence in intron 15 and repeated sequences of the Alu family in introns 14 and 17. These repeated sequences most likely represent molecular fossils of ancient DNA elements which were involved in such a recombination event.
Correspondence to: M. Pauly 相似文献