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101.
An intact enteric nervous system is required for normal gastrointestinal tract function. Several human conditions result from decreased innervation by enteric neurons; however, the genetic basis of enteric nervous system development and function is incompletely understood. In an effort to increase our understanding of the mechanisms underlying enteric nervous system development, we screened mutagenized zebrafish for changes in the number or distribution of enteric neurons. We also established a motility assay and rescreened mutants to learn whether enteric neuron number is correlated with gastrointestinal motility in zebrafish. We describe mutations isolated in our screen that affect enteric neurons specifically, as well as mutations that affect other neural crest derivatives or have pleiotropic effects. We show a correlation between the severity of enteric neuron loss and gastrointestinal motility defects. This screen provides biological tools that serve as the basis for future mechanistic studies. 相似文献
102.
103.
The omptins are a family of enterobacterial surface proteases/adhesins that share high sequence identity and a conserved beta-barrel fold in the outer membrane. The omptins are multifunctional, and the individual omptins exhibit differing virulence-associated functions. The Pla plasminogen activator of Yersinia pestis contributes by several mechanisms to bacterial invasiveness and the systemic, uncontrolled proteolysis in plague. Pla proteolytically activates the human proenzyme plasminogen and inactivates the antiprotease alpha2-antiplasmin, and its binding to laminin localizes the uncontrolled plasmin activity onto basement membranes. These properties enhance bacterial migration through tissue barriers. Pla also degrades circulating complement proteins and functions in bacterial invasion into human epithelial cells. PgtE of Salmonella enterica and OmpT of Escherichia coli have been shown to degrade cationic antimicrobial peptides from epithelial cells or macrophages. PgtE and SopA of Shigella flexneri appear important in the intracellular phases of salmonellosis and shigellosis, whereas functions of OmpT have mainly been associated with protein degradation in E. coli cells. The differing virulence roles and functions have been attributed to minor sequence variations at the surface-exposed regions important for substrate recognition, to the dependence of omptin functions on lipopolysaccharide, and to the different regulation of omptin expression. 相似文献
104.
Prime SS Eveson JW Stone AM Huntley SP Davies M Paterson IC Robinson CM 《The Journal of pathology》2004,203(4):927-932
This study examined the behaviour of nine human malignant oral keratinocyte cell lines following orthotopic transplantation to the floor of the mouth of athymic mice. Tumourigenesis, local spread, and metastatic dissemination were correlated with known cellular responses to transforming growth factor-beta 1 (TGF-beta 1). Six of nine cell lines were tumourigenic; four of these cell lines showed local spread which was characterized by vascular and bone invasion. Metastatic spread was uncommon, with only 9% of animals with primary tumours developing metastases and these were almost exclusively found in the regional lymph nodes; there was one pulmonary metastasis and no liver deposits. Tumour cell behaviour did not reflect the clinical stage of the original tumours. Cell lines that were resistant to TGF-beta 1-induced growth inhibition were more likely to form primary tumours, exhibit local spread, and metastasize than cells that were growth-inhibited by the ligand. The data demonstrate that tumourigenicity and tumour behaviour in this orthotopic mouse model varied between cell lines and that the pattern of local invasion and metastasis was similar to that seen in human oral cancer. Furthermore, cell lines that were refractory to the growth inhibitory effects of TGF-beta 1 behaved more aggressively than cells that underwent ligand-induced cell-cycle arrest. 相似文献
105.
Characteristics of human neural stem cells In Vitro and after transplantation into rat brain 总被引:6,自引:0,他引:6
Aleksandrova MA Podgornyi OV Marei MV Poltavtseva RA Tsitrin EB Gulyaev DV Cherkasova LV Revishchin AV Korochkin LI Khrushchov NG Sukhikh GN 《Bulletin of experimental biology and medicine》2005,139(1):114-120
We studied the effect of culturing conditions on the fate of human neural stem cells after transplantation into rat brain. Human neural stem cells cultured in the presence of mitogens without LIF migrated along the ependyma and cerebral vessels of recipients, but to a great extent degenerated by the 20th day after transplantation. Neural stem cells cultured with LIF migrated, apart from the above mentioned pathways, in the cortex and hippocampus, well survived; proliferating cells were retained 30 days after transplantation.__________This revised version was published online in July 2005 with the addition of the issue title and article categoryTranslated from Kletochnye Tekhnologii v Biologii i Meditsine, Vol. 1, No. 1, pp. 13–19, January, 2005 相似文献
106.
Myriam Polette Christine Gilles Sophie de Bentzmann Dieter Gruenert Jean-Marie Tournier Philippe Birembaut 《Clinical & experimental metastasis》1998,16(2):105-112
The acquisition of a metastatic phenotype by epithelial cells implicates a series of changes altering their differentiation, their overall behavior and morphology. In the present study, we have examined the relationships between the cellular morphology, E-cadherin expression, matrix metalloproteinases expression and in vitro invasive properties in two human bronchial immortalized cell lines. The (16HBE14o-) cell line which did not show any invasive abilities in the Boyden chamber assay displayed a typical epithelial morphology in monolayer, expressed high levels of E-cadherin and synthesized neither MMP-2 and MT1-MMP nor vimentin. In contrast, the BZR cell line which was highly invasive displayed a more elongated phenotype in monolayer, did not produce E-cadherin but expressed vimentin, MMP-2 and MT1-MMP. Our data therefore suggest that the metastatic progression of broncho-pulmonary cancer cells results in a cellular dedifferentiation and the gain of some mesenchymal attributes (loss of E-cadherin and expression of vimentin) associated with enhanced degradative properties (expression of metalloproteinases).© Rapid Science 1998 相似文献
107.
Kiyosumi Shibata Fumitaka Kikkawa Akihiko Nawa Koji Tamakoshi Nobuhiko Suganuma Yutaka Tomoda 《Clinical & experimental metastasis》1997,15(6):612-619
Ovarian cancer cells disseminate by attachment to the peritoneal mesothelial cell surface of the abdominal cavity. We therefore investigated the influence of conditioned medium (CM) from human peritoneal tissues and mesothelial cells on the secretion of matrix metalloproteinases (MMPs) by ovarian cancer cells. The molecular weights of MMPs stimulating factors derived from human peritoneal tissues and mesothelial cells were estimated using microconcentrators with various cut-off membranes. Human peritoneal tissues were obtained from 12 surgical patients, and mesothelial cells were isolated from three peritoneal specimens. Exposure to CM from peritoneal tissue caused a concentration-dependent increase of the MMP-2 and MMP-9 bands in CM from NOM1 ovarian cancer cells, as shown by zymography. There was a significant difference in the increase of MMP-2 and MMP-9 (2.46-fold and 7.14-fold, respectively, at 0.4mg/ml protein; P < 0.005). CM from mesothelial cells also significantly increased the secretion of MMP-9 by NOM1 cells. The molecular size of possible MMP-9-stimulating factors secreted by peritoneal tissues and mesothelial cells was above M 100000. Further, CM of peritoneal tissues and mesothelial cells also induced the invasiveness of NOM1 cells. These findings suggest that mesothelial cells may secrete some factors which predominantly induce the MMP-9 production and increase invading cell numbers. 相似文献
108.
Brooks TD Slomp J Quax PH De Bart AC Spencer MT Verheijen JH Charlton PA 《Clinical & experimental metastasis》2000,18(6):445-453
Recent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression.
The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies
to PAI-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma
cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also
attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not express
uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive
phenotype, which was again attenuated by MAI- 12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells
to vitronectin, the antibody to uPA reduced their attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell
adhesion (IC50 180nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPA variant, which had
an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importance
of a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also
suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent
detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation
of PAI-1 activity may be of therapeutic benefit for the treatment of cancer.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
109.
110.
Douglas A. Weeks Richelle L. Malott Craig W. Zuppan Boleslaw H. Liwnicz J. Bruce Beckwith 《Ultrastructural pathology》1994,18(1):23-28
The rhabdoid tumor (RT) was first described as an aggressive neoplasm of unknown histogenesis affecting the kidneys of infants and young children, but has since been reported in all ages and in many other primary sites, including the central nervous system. It has been shown, however, that the histologic and cytologic features of RT can be mimicked by many other tumors of known histogenesis. For this and other reasons it remains controversial whether cases of putative extrarenal RT represent the same histogenetic entity as RT of the kidney (RTK), another entity or entities, or merely a diverse collection of unrelated tumors sharing a common morphologic phenotype. The present paper describes a lethal primary cerebral tumor in a 26-month-old Hispanic boy that was composed predominantly of cells exhibiting the “classic” rhabdoid phenotype by light microscopy. lmmunocytochemical and ultrastructural studies disclosed features of primitive neuroglial differentiation not seen in RTK. The findings in this case, as well as evidence from other studies, would seem to support the notion that primary RT of the brain may in fact constitute a morphologic and clinicopathologic entity. However, hat entity likely represents a distinctive type of neuroglial neoplasm, more closely related t o other primitive brain tumors than t o RTK. 相似文献