全文获取类型
收费全文 | 8252篇 |
免费 | 872篇 |
国内免费 | 5篇 |
出版年
2022年 | 55篇 |
2021年 | 69篇 |
2019年 | 60篇 |
2018年 | 81篇 |
2017年 | 60篇 |
2016年 | 141篇 |
2015年 | 222篇 |
2014年 | 271篇 |
2013年 | 361篇 |
2012年 | 453篇 |
2011年 | 418篇 |
2010年 | 311篇 |
2009年 | 291篇 |
2008年 | 470篇 |
2007年 | 473篇 |
2006年 | 417篇 |
2005年 | 432篇 |
2004年 | 444篇 |
2003年 | 455篇 |
2002年 | 385篇 |
2001年 | 147篇 |
2000年 | 114篇 |
1999年 | 124篇 |
1998年 | 125篇 |
1997年 | 82篇 |
1996年 | 94篇 |
1995年 | 78篇 |
1994年 | 97篇 |
1993年 | 94篇 |
1992年 | 107篇 |
1991年 | 93篇 |
1990年 | 88篇 |
1989年 | 86篇 |
1988年 | 81篇 |
1987年 | 84篇 |
1986年 | 96篇 |
1985年 | 106篇 |
1984年 | 108篇 |
1983年 | 91篇 |
1982年 | 90篇 |
1981年 | 81篇 |
1980年 | 77篇 |
1979年 | 86篇 |
1978年 | 66篇 |
1977年 | 69篇 |
1976年 | 60篇 |
1975年 | 56篇 |
1974年 | 72篇 |
1973年 | 57篇 |
1972年 | 52篇 |
排序方式: 共有9129条查询结果,搜索用时 31 毫秒
961.
Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on insights that have emerged from the genetic analysis of long-distance axonal transport between the cell body and the synaptic terminal. We also discuss recent genetic evidence that supports the hypothesis that disruptions in axonal transport may cause or dramatically contribute to neurodegenerative diseases. 相似文献
962.
963.
Inflammation surrounding implantable glucose sensors may be controlled through local release of dexamethasone at the site of implantation. In the present study, we evaluated the distribution of dexamethasone in rat subcutaneous tissue during the first 2.5 days after local release. Osmotic pumps containing [3H]dexamethasone were implanted into the subcutaneous tissue of rats. Digital autoradiography was used to measure the distribution of the [3H]dexamethasone within the subcutaneous tissue at 6, 24, and 60 h after implantation. Measured concentration profiles, near the catheter tip through which the agent was released, were compared to mathematical models of drug diffusion and elimination. The results demonstrate that the majority of the [3H]dexamethasone delivered into the subcutaneous tissue was found within a 3 mm region surrounding the catheter tip. There was good agreement between the experimental data and the mathematical model. The diffusion coefficient for dexamethasone in subcutaneous tissue was found to be D = 4.11 +/- 1.77 x 10(-10) m2/s, and the elimination rate constant was found to be k = 3.65 +/- 2.24 x 10(-5) s(-1). The diffusion coefficient and elimination rate constants for dexamethasone in subcutaneous tissue have not been previously reported. The use of a mathematical model may be useful in predicting the effectiveness of local delivery of dexamethasone around implantable glucose sensors. 相似文献
964.
Group B Streptococcus: global incidence and vaccine development 总被引:1,自引:0,他引:1
Johri AK Paoletti LC Glaser P Dua M Sharma PK Grandi G Rappuoli R 《Nature reviews. Microbiology》2006,4(12):932-942
An ongoing public health challenge is to develop vaccines that are effective against infectious diseases that have global relevance. Vaccines against serotypes of group B Streptococcus (GBS) that are prevalent in the United States and Europe are not optimally efficacious against serotypes common to other parts of the world. New technologies and innovative approaches are being used to identify GBS antigens that overcome serotype-specificity and that could form the basis of a globally effective vaccine against this opportunistic pathogen. This Review highlights efforts towards this goal and describes a template that can be followed to develop vaccines against other bacterial pathogens. 相似文献
965.
Pollution is a worldwide problem and its potential to influence the physiology of human populations is great. Studies of human growth and development in relation to pollution have increased in number and quality since the mid-twentieth century. Many studies have found that some pollutants have detrimental effects on human growth, particularly prenatal growth. The heavy metal, lead, is commonly found in human populations and is related to smaller size at birth and studies have reported decrements that range up to about 200 grams. Noise stress from transportation sources also is related to reduced prenatal growth with somewhat smaller decrements reported. Studies of humans exposed to polychlorinated biphenyls, one of the persistent organic pollutants, have reduced size at birth, advanced sexual maturation and altered hormone levels related to thyroid regulation. Thus different pollutants exert effects through different physiological pathways. However, some studies have not observed these effects, which indicates that the situation is complex and requires further study with better study designs. Determining the effects of pollutants on human physiology and growth is difficult as it requires fairly large numbers of subjects who are not purposely exposed but for whom exposure can be measured. These effects of pollutants and the mechanisms of effect require further study to understand and, it is hoped, to blunt or block any detrimental effects on human health and well-being. 相似文献
966.
Houtman JC Yamaguchi H Barda-Saad M Braiman A Bowden B Appella E Schuck P Samelson LE 《Nature structural & molecular biology》2006,13(9):798-805
Receptor oligomerization is vital for activating intracellular signaling, in part by initiating events that recruit effector and adaptor proteins to sites of active signaling. Whether these distal molecules themselves oligomerize is not well appreciated. In this study, we examined the molecular interactions of the adaptor protein GRB2. In T cells, the SH2 domain of GRB2 binds phosphorylated tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL. Using biochemical and biophysical techniques in conjunction with confocal microscopy, we observed that the simultaneous association of GRB2, via its SH2 and SH3 domains, with multivalent ligands led to the oligomerization of these ligands, which affected signaling. These data suggest that multipoint binding of distal adaptor proteins mediates the formation of oligomeric signaling clusters vital for intracellular signaling. 相似文献
967.
Brian M. Olson Thomas P. Frye Laura E. Johnson Lawrence Fong Keith L. Knutson Mary L. Disis Douglas G. McNeel 《Cancer immunology, immunotherapy : CII》2010,59(6):943-953
Prostatic acid phosphatase (PAP) has been investigated as the target of several antigen-specific anti-prostate tumor vaccines.
The goal of antigen-specific active immunotherapies targeting PAP would ideally be to elicit PAP-specific CD8+ effector T
cells. The identification of PAP-specific CD8+ T-cell epitopes should provide a means of monitoring the immunological efficacy
of vaccines targeting PAP, and these epitopes might themselves be developed as vaccine antigens. In the current report, we
hypothesized that PAP-specific epitopes might be identified by direct identification of pre-existing CD8+ T cells specific
for HLA-A2-restricted peptides derived from PAP in the blood of HLA-A2-expressing individuals. 11 nonamer peptides derived
from the amino acid sequence of PAP were used as stimulator antigens in functional ELISPOT assays with peripheral blood mononuclear
cells from 20 HLA-A2+ patients with prostate cancer or ten healthy blood donors. Peptide-specific T cells were frequently
identified in both groups for three of the peptides, p18–26, p112–120, and p135–143. CD8+ T-cell clones specific for three
peptides, p18–26, p112–120, and p299–307, confirmed that these are HLA-A2-restricted T-cell epitopes. Moreover, HLA-A2 transgenic
mice immunized with a DNA vaccine encoding PAP developed epitope-specific responses for one or more of these three peptide
epitopes. We propose that this method to first identify epitopes for which there are pre-existing epitope-specific T cells
could be used to prioritize MHC class I-specific epitopes for other antigens. In addition, we propose that the epitopes identified
here could be used to monitor immune responses in HLA-A2+ patients receiving vaccines targeting PAP to identify potentially
therapeutic immune responses. 相似文献
968.
Gianfranco Balboni Erika Marzola Yusuke Sasaki Akihiro Ambo Ewa D. Marczak Lawrence H. Lazarus Severo Salvadori 《Bioorganic & medicinal chemistry》2010,18(16):6024-6030
Here we evaluated how the interchange of the amino acids 2′,6′-dimethyl-l-tyrosine (Dmt), 2′,6′-difluoro-l-tyrosine (Dft), and tyrosine in position 1 can affect the pharmacological characterization of some reference opioid peptides and pseudopeptides. Generally, Dft and Tyr provide analogues with a similar pharmacological profile, despite different pKa values. Dmt/Tyr(Dft) replacement gives activity changes depending on the reference opioid in which the modification was made. Whereas, H-Dmt-Tic-Asp1-Bid is a potent and selective δ agonist (MVD, IC50 = 0.12 nM); H-Dft-Tic-Asp1-Bid and H-Tyr-Tic-Asp1-Bid are potent and selective δ antagonists (pA2 = 8.95 and 8.85, respectively). When these amino acids are employed in the synthesis of deltorphin B and its Dmt1 and Dft1 analogues, the three compounds maintain a very similar δ agonism (MVD, IC50 0.32–0.53 nM) with a decrease in selectivity relative to the Dmt1 analogue. In the less selective H-Dmt-Tic-Gly1-Bid the replacement of Dmt with Dft and Tyr retains the δ agonism but with a decrease in potency. Antagonists containing the Dmt-Tic pharmacophore do not support the exchange of Dmt with Dft or Tyr. 相似文献
969.
Lawrence D. Harder Marcelo A. Aizen 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1539):529-543
Pollen limitation (PL) of seed production creates unique conditions for reproductive adaptation by angiosperms, in part because, unlike under ovule or resource limitation, floral interactions with pollen vectors can contribute to variation in female success. Although the ecological and conservation consequences of PL have received considerable attention in recent times, its evolutionary implications are poorly appreciated. To identify general influences of PL on reproductive adaptation compared with those under other seed-production limits and their implications for evolution in altered environments, we derive a model that incorporates pollination and post-pollination aspects of PL. Because PL always favours increased ovule fertilization, even when population dynamics are not seed limited, it should pervasively influence selection on reproductive traits. Significantly, under PL the intensity of inbreeding does not determine whether outcrossing or autonomous selfing can evolve, although it can affect which response is most likely. Because the causes of PL are multifaceted in both natural and anthropogenically altered environments, the possible outcrossing solutions are diverse and context dependent, which may contribute to the extensive variety of angiosperm reproductive characteristics. Finally, the increased adaptive options available under PL may be responsible for positive global associations between it and angiosperm diversity. 相似文献
970.
Paul John L. Geraldino Rafael Riosmena‐Rodriguez Lawrence M. Liao And Sung Min Boo 《Journal of phycology》2010,46(2):336-345
Species discrimination within the gigartinalean red algal genus Hypnea has been controversial. To help resolve the controversy and explore phylogeny within the genus, we determined rbcL sequences from 30 specimens of 23 species within the genus, cox1 from 22 specimens of 10 species, and psaA from 16 species. We describe H. caespitosa as a new species characterized by a relatively slender main axis; a pulvinate growth habit with entangled, anastomosing, and subulate uppermost branches; and unilaterally borne tetrasporangial sori. The new species occurs in the warm waters of Malaysia, the Philippines, and Singapore. The phylogenetic trees of rbcL, psaA, and cox1 sequences showed a distant relationship of H. caespitosa to H. pannosa J. Agardh from Baja California and the marked differentiation from other similar species. The rbcL + psaA tree supported monophyly of the genus with high bootstrap values and posterior probabilities. The analysis revealed three clades within the genus, corresponding to three sections, namely, Virgatae, Spinuligerae, and Pulvinatae first recognized by J. G. Agardh. Exceptions were H. japonica T. Tanaka in Pulvinatae and H. spinella (C. Agardh) Kütz. in Spinuligerae. 相似文献